Category Archives: Embryonic Stem Cells

‘Self-eating’ stem cell process may be the key to new regenerative therapies – Penn Today

The self-eating process in embryonic stem cells known as chaperone-mediated autophagy (CMA) and a related metabolite may serve as promising new therapeutic targets to repair or regenerate damaged cells and organs,Penn Medicineresearchers show in a new study published online inScience.

Human bodies contain more than 200 different types of specialized cells. All of them can be derived from embryonic stem (ES) cells, which relentlessly self-renew while retaining the ability to differentiate into any cell type in adult animals, a state known as pluripotency. Researchers have known that the cells metabolism plays a role in this process; however, it wasnt clear exactly how the cells internal wiring works to keep that state and ultimately decide stem cell fate.

The new preclinical study, for the first time, shows how the stem cells keeps CMA at low levels to promote that self-renewal, and when the stem cell is ready, it switches that suppression off to enhance CMA, among other activities, and differentiate into specialized cells.

Its an intriguing discovery in the field of stem cell biology and for researchers looking to develop therapies for tissue or organ regeneration, says senior authorXiaolu Yang, a professor of cancer biology at the Abramson Family Cancer Research Institute in the Perelman School of Medicine. We reveal two novel ways to potentially manipulate the self-renewal and differentiation of stem cells: CMA and a metabolite, known as alpha-ketoglutarate, that is regulated by CMA. Rationally intervening or guiding these functions could be a powerful way to increase the efficiency of regenerative medicine approaches.

This story is by Melissa Moody. Read more at Penn Medicine News.

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'Self-eating' stem cell process may be the key to new regenerative therapies - Penn Today

Researchers Discover a New Side of Cancer that May Explain Its Resistance to Treatment – Genetic Engineering & Biotechnology News

Cancers ability to resist chemotherapy has been a roadblock to achieving lasting remissions or cures. Scientists have believed that unique genetic mutations in tumors may be to blame for drug resistance. However, they are starting to look at nongenetic changes in cancer cells to explain their adaptability. An example of this is cancers ability to change its identity. A prostate cancer cell that is sensitive to hormone-blocking therapy might change into a cell type that does not require the hormone for its growth. This heterogeneity creates obstacles for treatment, since a single drug is unlikely to work against so many different cell types.

Now, a team of researchers at the Sloan Kettering Institute (SKI), the Koch Institute for Integrative Cancer Research at MIT, and the Klarman Cell Observatory at the Broad Institute have discovered that this tumor heterogeneity can be traced back to a common source: a particularly flexible cell state that is characteristic of a subset of cells in a tumor and can generate many other diverse cell types.

Their study, Emergence of a High-Plasticity Cell State during Lung Cancer Evolution, is published in Cancer Cell and led by Tuomas Tammela, MD, PhD, an assistant member in the cancer biology and genetics program at SKI.

The high-plasticity cell state is the starting point for much of the heterogeneity we see in tumors, stated Tammela. Its kind of like a busy intersection of many roads: Wherever a cell wants to end up identity-wise, it has to go through this cell state.

Tumor evolution from a single cell into a malignant, heterogeneous tissue remains poorly understood. Here, we profile single-cell transcriptomes of genetically engineered mouse lung tumors at seven stages, from pre-neoplastic hyperplasia to adenocarcinoma, the researchers wrote.

This highly plastic cell state is something completely new, stated Jason Chan, MD, PhD, a physician-scientist doing a fellowship in the Tammela lab and one of the papers lead authors. When we saw it, we didnt know what it was because it was so different. It didnt look like normal lung cells where the cancer came from, and it didnt really look like lung cancer either. It had features of embryonic germ layer stem cells, cartilage stem cells, and even kidney cells, all mixed together.

The researchers observed these cells in every tumor they examined and identified these highly plastic cells by single cell RNA sequencing (scRNA-Seq). By performing scRNA-Seq on tumors as they grew over time, the researchers were able to observe when and how different cell types emerged over the course of a tumors evolution. From these data, the researchers were able to create a kind of map of which cells came from which other cells.

The map contains major highways and little dirt roads, Tammela explained. The high-plasticity cell state that we identified sits right in the middle of the map. It has a lot of paths coming in, and it has even more paths coming out.

This high-plasticity cell state emerged consistently in a tumors evolution and persisted throughout its growth.

Stem cells play important roles in embryonic development and in tissue repair. Many scientists think that cancers arise from specific cancer stem cells. But Tammela and colleagues do not think these high-plasticity cells are stem cells. Unlike stem cells, the cells are not present at the very beginning of a tumors growth, and emerge later.

When we compare the gene expression signature of these highly plastic cells to normal stem cells or known cancer stem cells, the signatures dont match at all. They look completely different, he said.

Cancer cells progressively adopt alternate lineage identities, computationally predicted to be mediated through a common transitional, high-plasticity cell state (HPCS). Accordingly, HPCS cells prospectively isolated from mouse tumors and human patient-derived xenografts display high capacity for differentiation and proliferation. The HPCS program is associated with poor survival across human cancers and demonstrates chemoresistance in mice. Our study reveals a central principle underpinning intra-tumoral heterogeneity and motivates therapeutic targeting of the HPCS, noted the researchers.

Our model could explain why certain cancer cells are resistant to therapy and dont have a genetic basis for that resistance that we can identify, Chan stated.

Chan also explained it is not all the cells in the tumor that are adapting, but a subset of the cancer cells that are just more malleable.

The researchers believe it may be possible to avert the emergence of resistance and provide lasting remission by combining chemotherapy drugs with new medications that target these highly plastic cells.

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Researchers Discover a New Side of Cancer that May Explain Its Resistance to Treatment - Genetic Engineering & Biotechnology News

"Self-eating" Process of Stem Cells May be Key to New Regenerative Therapies – Mirage News

Translucently colored embryonic stem (ES) cell (upper right) and its differentiating derivatives (left and lower right). The small round bodies inside cells represent lysosomes, with the pink color indicating ones that are undergoing chaperone-mediated autophagy (CMA), a selective form of autophagy that is demonstrated only in mammals. CMA governs the balance between self-renewal and differentiation of ES cells. It is kept at low levels in undifferentiated ES cells to maintain the pluripotent state. Upon induction of differentiation, CMA flux increases due to the reduction of pluripotency factors, leading to changes in cellular metabolism and epigenetic landscape that favor differentiation.

PHILADELPHIAThe self-eating process in embryonic stem cells known as chaperone-mediated autophagy (CMA) and a related metabolite may serve as promising new therapeutic targets to repair or regenerate damaged cells and organs, Penn Medicine researchers show in a new study published online in Science.

Human bodies contain over 200 different types of specialized cells. All of them can be derived from embryonic stem (ES) cells, which relentlessly self-renew while retaining the ability to differentiate into any cell type in adult animals, a state known as pluripotency. Researchers have known that the cells metabolism plays a role in this process; however, it wasnt clear exactly how the cells internal wiring works to keep that state and ultimately decide stem cell fate.

The new preclinical study, for the first time, shows how the stem cells keeps CMA at low levels to promote that self-renewal, and when the stem cell is ready, it switches that suppression off to enhance CMA, among other activities, and differentiate into specialized cells.

Its an intriguing discovery in the field of stem cell biology and for researchers looking to develop therapies for tissue or organ regeneration, said senior author Xiaolu Yang, PhD, a professor of Cancer Biology at the Abramson Family Cancer Research Institute in the Perelman School of Medicine at the University of Pennsylvania. We reveal two novel ways to potentially manipulate the self-renewal and differentiation of stem cells: CMA and a metabolite, known as alpha-ketoglutarate, that is regulated by CMA. Rationally intervening or guiding these functions could be a powerful way to increase the efficiency of regenerative medicine approaches.

Autophagy is a cell-eating mechanism necessary for survival and function of most living organisms. When cells self-eat, the intracellular materials are delivered to lysosomes, which are organelles that help break down these materials. There are a few forms of autophagy. However, unlike the other forms, which are present in all eukaryotic cells, CMA is unique to mammals. To date, the physiological role of CMA remains unclear.

Using metabolomic and genetic laboratory techniques on the embryonic stem cells of mice, the researchers sought to better understand significant changes that took place during their pluripotent state and subsequent differentiation.

They found that CMA activity is kept at a minimum due to two cellular factors critical for pluripotencyOct4 and Sox2that suppresses a gene known as LAMP2A, which provides instructions for making a protein called lysosomal associated membrane protein-2 necessary in CMA. The minimal CMA activity allows stem cells to maintain high levels of alpha-ketoglutarate, a metabolite that is crucial to reinforce a cells pluripotent state, the researchers found.

When its time for differentiation, the cells begin to upregulate CMA due to the reduction in Oct4 and Sox2. Augmented CMA activity leads to the degradation of key enzymes responsible for the production of alpha-ketoglutarate. This leads to a reduction in alpha-ketoglutarate levels as well as an increases in other cellular activities to promote differentiation. These findings reveal that CMA and alpha-ketoglutarate dictate the fate of embryonic stem cells.

Embryonic stem cells are often called pluripotent due to their remarkable ability to give rise to every cell type in the body, except the placenta and umbilical cord. Embryonic stem cells not only provide a superb system to study early mammalian development, but also hold great promise for regenerative therapies to treat various human disorders. The development of stem-cell based regenerative medicine therapies has rapidly increased in the last decade, with several approaches in studies shown to repair damaged heart tissue, replace cells in solid organ transplantation, and in some cases address neurological disorders.

This newly discovered role of autophagy in the stem cell is the beginning of further investigations that could lead to researchers and physician-scientists to better therapies to treat various disorders, Yang said.

Penn co-authors of the study include the first author Yi Xu, a post-doctoral researcher in Yangs Lab, Yang Zhang and Sixiang Yu, also in Yangs lab, Lili Guo and Ian A. Blair of the department of Systems Pharmacology and Translational Therapeutics, Mengyuan Kan of the department of Biostatistics, Epidemiology and Informatics, as well as Juan C. Garca-Caaveras and Joshua D. Rabinowitz of Princeton University.

The study was supported the National Institutes of Health (R01CA182675, R01CA184867, R01CA235760, and P30ES013508, and the Department of Defense (W81XWH-15-1-0678).

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"Self-eating" Process of Stem Cells May be Key to New Regenerative Therapies - Mirage News

Letters to editor: Sundial Bridge gathering, Donald Trump and COVID-19 – Record Searchlight

Redding Record Searchlight Published 8:00 a.m. PT July 26, 2020

Worshippers came to Redding's Sundial Bridge on July 22, 2020. The crowd put the community 'at risk' for COVID-19, Shasta County health officials say. Redding Record Searchlight

I am appalled and dismayed at thegathering at the Sundial Bridge earlier this week. First, it's unconscionable to gather hundreds of people during a pandemic, no masks or distancing in place.Second, no permit was issued for this gathering, nor was one applied for. The lack of responsibility for this event is amazing.Did no one know about it?Well, all those attendees certainly did, so it seems unlikely that the higher-ups at Bethel didn't, and apparently they made no effort to stop this travesty.Sean Feucht, the alleged organizer, has had events like this recently in other counties in California completely disregarding the health of the communities he gathers in.Christian?I think not.The disregard for local citizens and our community is quite apparent. We live in a rural area.It's helped us stay off the State Watch List, so more businesses can stay open.There are so many small businesses struggling to keep afloat and then a stunt like this is pulled that jeopardized everyone's health.Where were the police?Did no one in city government know about this? When the spike in COVID-19cases comes, it will be because of this unlawful, unnecessary gathering.

Hazel Hughes,Redding

The GOP has long sustained a frontal attack on the ultimate value of science to society. In 2016, national alarms sounded as science marches rang bells with gangs of teachers, liberal arts sympathizers, and mobs of parents, kids, scientists, librarians, researchers, and servers marching to protest. Fiftyyears ago Richard Nixon established the EPA. He put weight behind the GOPs previous value of an old Greek proverbs essence - A society grows great when old men plant trees whose shade they know they shall never sit in. And then the Republican party changed. Again and again. From creationism, opposition to embryonic stem cells, attempting to link abortion with breast cancer and mental illness, rejecting contraception while absolving itself of millions of unplanned pregnancies for society to absorb, to global warming, the GOP became something new. Today it is the spectacle, foolishness, and mockery displayed almost daily. Science isnt infallible. But it always gives the best odds towards truth in all it seeks in earnest. It is always playing the best odds. Carl Sagan called science a candle in the dark." Dont let the light go out. Restore scientific integrity to the federal government. Insist upon representatives who richly value science.

Max Walter, Redding

Regarding the recent Back the Blue rally: I think it was a great idea. I think most of us have great respect for the police, just not those few who make them look bad. I support Black Lives Matter and peaceful protests.I am against using riot police, mace, clubs, and shields against peaceful protesters. I am against police brutality and brutality inflicted by citizens against each other and the police. I am against police disguised in camo hauling people into unmarked vans like is happening, as I speak, in Portland, Oregon. I am against rioting and property damage by individuals who scream their support for a cause but are using it to engage in disruptive and damaging behavior and are behaving in a way that justifies police action. I believe that the use of deadly force should be exceedingly rare. I believe police unions are allowing bad police to stay on the job.All of these beliefs are not mutually exclusive nor should they be politicized into for or against police or protesters.

Joyce Lively, Redding

The key to stopping the COVID-19economy from turning into a major depression is what President Trump has already started: reducing government regulatory control of the economy and letting thefree market self-correct. This is what President Harding did during thedepression of 1920-21. The economy roared back.Contrarily, President Roosevelt instituted every Marxist and unconstitutional control on the economy as possible during the depression that started in 1929 and the downturn lasted 13 years.If it were not for the huge increase in output for World War II, who knows how long it would have lasted. Secondly, I see nothing but COVID-19ignorance caused by pronouncements from our politically corrupthealth agencies. First, masks worn by everyone will not keep anyone from contracting COVID-19 only properly fitted respirators will. And that is the problem with dictating mask use. It makes the few who are vulnerable to death from COVID-19 come out from self-quarantine where they should stay.

Carl Reed, Igo

Have we become a nation of anger? Reminds me of a 2-year-old throwing a tantrum, and then the parents give in to the child's demands. What happened to counting from one to 10 to calm down? If you feel you've suffered an injustice, does that give you the right to burn, loot, and injure anyone and anything? And who pays for the destroyed police cars and burned buildings? The hard-working taxpayers in this country. Take positive action. If you feel the police are not doing a good job, why don't you become a policeman and show everyone how to perform fairly. President Kennedy said, "Ask not what your country can do for you - ask what you can do for your country." Martin Luther King Jr.'swords were "I have a dream that my four little children will one day live in a nation where they will not be judged by the color of their skin, but by the content of their character. How is your character?

Miriam Johnson, Redding

We have a national pandemic that has killed 140,000-pluspeople nationwide and 7,697-plusin California and all State Sen. Brian Dahle is concerned about is the governor re-shutting down small businesses in the state because the coronavirus infection and death rates exploded. The governor had to do this because people did not practice the recommended safety measures that minimize spreading the coronavirus and businesses did not enforce them.Dahle tells us that people should be able to decide for themselves what is best to prevent catching the coronavirus and that wearing breathing masks should be left up to personal choice according to a July 14 Record Searchlight story.If everyone had practiced the recommended safety measures the impact on business would have been significantly lower. Dahle doesnt understand this simple concept. Dahles ideas are making matters worse. This November we need to get rid of Dahle and replace him with Pamela Swartz who has the ability to find solutions to important issues.

Tom Laurent,Yreka

On July 17, I loaded my car with items bought from Walmart and left my purse in the cart, realized about 10 minutes later after driving off, what I had done, returned to Walmart and checked with customer service and they had my purse. I want to thank the good person that did this kindness and turned it in.

Polly Thomson, Redding

There's this constant push from President Trump along withSecretary of Education, Betsy DeVos,to fully reopen our schools just as they were before the pandemic. If my biology teacher were still alive, I can hear her exclaiming, "You'll not put my studentsin a petri dish!"Before this latest push, our president had led the way to demand that businesses return to normal so we got the wild and crowded beach parties along with bars fully open and serving up drinks, etc.As predicted by the experts,these moves were followedshortly by a stunning increase in the spread of the virus. If we follow Trump, we will literally be drinking away our kid's futures. If we all succumb to the Trump-DeVosSyndrome,it's very likely that our country will be hit with permanent damage

Parker Pollock, Redding

The Roman Empire survived for 2,500 years, plus or minus, America has lasted 250, plus or minus, and are there any comparisons to be drawn? The madness on our streets and those who are the perpetrators have the same M.O. as those of Rome. There are also the rioters that led to the Russian Revolution, The Red Army revolt, and most hostile takeovers throughout history. Stir up the youth with propaganda and false promises and let their Utopian lusts do the rest. What is taking place in America today had warning signs for the last 100 years as our government started dismantling our Constitution and Bill of Rights. Using the same "Cosmic Morality" that is being used today we were slowly led down the "entitlement" passageway until it firmly coupled with the Marxist promise of "Equality for all through communism." If you don't like America now folks you will hate what is waiting in the wings. Why are they destroying your past, your language, your ethics, your faith, your future? Because people without a past cannot learn from or dictate their future without a past.

Vernon Packer, Redding

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Letters to editor: Sundial Bridge gathering, Donald Trump and COVID-19 - Record Searchlight

Stem Cells Market Study for 2020 to 2026 Providing Information on Key Players, Growth Drivers and Industry Challenges|CCBC, Vcanbio, Boyalife – Owned

QY Research has Published Latest Trending Report on Global Stem Cells Market

Los Angeles, United State, The report titledGlobal Stem Cells Marketis one of the most comprehensive and important additions to QY Researchs archive of market research studies. It offers detailed research and analysis of key aspects of the global Stem Cells market. The market analysts authoring this report have provided in-depth information on leading growth drivers, restraints, challenges, trends, and opportunities to offer a complete analysis of the global Stem Cells market. Market participants can use the analysis on market dynamics to plan effective growth strategies and prepare for future challenges beforehand. Each trend of the global Stem Cells market is carefully analyzed and researched about by the market analysts.

Request Sample Report and Full Report TOC:https://www.qyresearch.com/sample-form/form/1436482/global-stem-cells-market

The Essential Content Covered in the GlobalStem Cells Market Report:

* Top Key Company Profiles. * Main Business and Rival Information * SWOT Analysis and PESTEL Analysis * Production, Sales, Revenue, Price and Gross Margin * Market Share and Size

Global Stem Cells Market is estimated to reach xxx million USD in 2020 and projected to grow at the CAGR of xx% during 2020-2026. According to the latest report added to the online repository of QY Research the Stem Cells market has witnessed an unprecedented growth till 2020. The extrapolated future growth is expected to continue at higher rates by 2025.

Top Players of Stem Cells Market are Studied: CCBC, Vcanbio, Boyalife, Beikebiotech,

The report provides a 6-year forecast (2020-2026) assessed based on how the Stem Cells market is predicted to grow in major regions likeUSA, Europe, Japan, China, India, Southeast Asia, South America, South Africa, Others.

Segmentation by Type:Umbilical Cord Blood Stem Cell Embryonic Stem Cell Adult Stem Cell Other

Segmentation by Application:Diseases Therapy Healthcare

Reasons to Buy this Report:

Table of Contents

Table of Contents 1 Report Overview

1.1 Study Scope

1.2 Key Market Segments

1.3 Players Covered: Ranking by Stem Cells Revenue

1.4 Market Analysis by Type

1.4.1 Global Stem Cells Market Size Growth Rate by Type: 2020 VS 2026

1.4.2 Umbilical Cord Blood Stem Cell

1.4.3 Embryonic Stem Cell

1.4.4 Adult Stem Cell

1.4.5 Other

1.5 Market by Application

1.5.1 Global Stem Cells Market Share by Application: 2020 VS 2026

1.5.2 Diseases Therapy

1.5.3 Healthcare 1.6 Study Objectives 1.7 Years Considered 2 Global Growth Trends by Regions

2.1 Stem Cells Market Perspective (2015-2026)

2.2 Stem Cells Growth Trends by Regions

2.2.1 Stem Cells Market Size by Regions: 2015 VS 2020 VS 2026

2.2.2 Stem Cells Historic Market Share by Regions (2015-2020)

2.2.3 Stem Cells Forecasted Market Size by Regions (2021-2026) 2.3 Industry Trends and Growth Strategy 2.3.1 Market Top Trends 2.3.2 Market Drivers

2.3.3 Market Challenges

2.3.4 Porters Five Forces Analysis

2.3.5 Stem Cells Market Growth Strategy

2.3.6 Primary Interviews with Key Stem Cells Players (Opinion Leaders) 3 Competition Landscape by Key Players

3.1 Global Top Stem Cells Players by Market Size

3.1.1 Global Top Stem Cells Players by Revenue (2015-2020)

3.1.2 Global Stem Cells Revenue Market Share by Players (2015-2020)

3.1.3 Global Stem Cells Market Share by Company Type (Tier 1, Tier 2 and Tier 3)

3.2 Global Stem Cells Market Concentration Ratio

3.2.1 Global Stem Cells Market Concentration Ratio (CR5 and HHI)

3.2.2 Global Top 10 and Top 5 Companies by Stem Cells Revenue in 2019

3.3 Stem Cells Key Players Head office and Area Served

3.4 Key Players Stem Cells Product Solution and Service

3.5 Date of Enter into Stem Cells Market

3.6 Mergers & Acquisitions, Expansion Plans 4 Breakdown Data by Type (2015-2026)

4.1 Global Stem Cells Historic Market Size by Type (2015-2020)

4.2 Global Stem Cells Forecasted Market Size by Type (2021-2026) 5 Stem Cells Breakdown Data by Application (2015-2026)

5.1 Global Stem Cells Market Size by Application (2015-2020)

5.2 Global Stem Cells Forecasted Market Size by Application (2021-2026) 6 North America

6.1 North America Stem Cells Market Size (2015-2020)

6.2 Stem Cells Key Players in North America (2019-2020)

6.3 North America Stem Cells Market Size by Type (2015-2020)

6.4 North America Stem Cells Market Size by Application (2015-2020) 7 Europe

7.1 Europe Stem Cells Market Size (2015-2020)

7.2 Stem Cells Key Players in Europe (2019-2020)

7.3 Europe Stem Cells Market Size by Type (2015-2020)

7.4 Europe Stem Cells Market Size by Application (2015-2020) 8 China

8.1 China Stem Cells Market Size (2015-2020)

8.2 Stem Cells Key Players in China (2019-2020)

8.3 China Stem Cells Market Size by Type (2015-2020)

8.4 China Stem Cells Market Size by Application (2015-2020) 9 Japan

9.1 Japan Stem Cells Market Size (2015-2020)

9.2 Stem Cells Key Players in Japan (2019-2020)

9.3 Japan Stem Cells Market Size by Type (2015-2020)

9.4 Japan Stem Cells Market Size by Application (2015-2020) 10 Southeast Asia

10.1 Southeast Asia Stem Cells Market Size (2015-2020)

10.2 Stem Cells Key Players in Southeast Asia (2019-2020)

10.3 Southeast Asia Stem Cells Market Size by Type (2015-2020)

10.4 Southeast Asia Stem Cells Market Size by Application (2015-2020) 11 India

11.1 India Stem Cells Market Size (2015-2020)

11.2 Stem Cells Key Players in India (2019-2020)

11.3 India Stem Cells Market Size by Type (2015-2020)

11.4 India Stem Cells Market Size by Application (2015-2020) 12 Central & South America

12.1 Central & South America Stem Cells Market Size (2015-2020)

12.2 Stem Cells Key Players in Central & South America (2019-2020)

12.3 Central & South America Stem Cells Market Size by Type (2015-2020)

12.4 Central & South America Stem Cells Market Size by Application (2015-2020) 13Key Players Profiles

13.1 CCBC

13.1.1 CCBC Company Details

13.1.2 CCBC Business Overview and Its Total Revenue

13.1.3 CCBC Stem Cells Introduction

13.1.4 CCBC Revenue in Stem Cells Business (2015-2020))

13.1.5 CCBC Recent Development

13.2 Vcanbio

13.2.1 Vcanbio Company Details

13.2.2 Vcanbio Business Overview and Its Total Revenue

13.2.3 Vcanbio Stem Cells Introduction

13.2.4 Vcanbio Revenue in Stem Cells Business (2015-2020)

13.2.5 Vcanbio Recent Development

13.3 Boyalife

13.3.1 Boyalife Company Details

13.3.2 Boyalife Business Overview and Its Total Revenue

13.3.3 Boyalife Stem Cells Introduction

13.3.4 Boyalife Revenue in Stem Cells Business (2015-2020)

13.3.5 Boyalife Recent Development

13.4 Beikebiotech

13.4.1 Beikebiotech Company Details

13.4.2 Beikebiotech Business Overview and Its Total Revenue

Continued here:
Stem Cells Market Study for 2020 to 2026 Providing Information on Key Players, Growth Drivers and Industry Challenges|CCBC, Vcanbio, Boyalife - Owned

Germ cell – Wikipedia

A germ cell is any biological cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate in the primitive streak and migrate via the gut of an embryo to the developing gonads. There, they undergo meiosis, followed by cellular differentiation into mature gametes, either eggs or sperm. Unlike animals, plants do not have germ cells designated in early development. Instead, germ cells can arise from somatic cells in the adult (such as the floral meristem of flowering plants).[1][2][3]

Multicellular eukaryotes are made of two fundamental cell types. Germ cells produce gametes and are the only cells that can undergo meiosis as well as mitosis. These cells are sometimes said to be immortal because they are the link between generations. Somatic cells are all the other cells that form the building blocks of the body and they only divide by mitosis. The lineage of germ cells is called germ line. Germ cell specification begins during cleavage in many animals or in the epiblast during gastrulation in birds and mammals. After transport, involving passive movements and active migration, germ cells arrive at the developing gonads. In humans, sexual differentiation starts approximately 6 weeks after conception. The end-products of the germ cell cycle are the egg or sperm.[4]

Under special conditions in vitro germ cells can acquire properties similar to those of embryonic stem cells (ES). The underlying mechanism of that change is still unknown. These changed cells are then called embryonic germ cells (EG). Both EG and ES are pluripotent in vitro, but only ES has proven pluripotency in vivo. Recent studies have demonstrated that it is possible to give rise to primordial germ cells from ES.[5]

There are two mechanisms to establish the germ cell lineage in the embryo. The first way is called preformistic and involves that the cells destined to become germ cells inherit the specific germ cell determinants present in the germ plasm (specific area of the cytoplasm) of the egg (ovum). The unfertilized egg of most animals is asymmetrical: different regions of the cytoplasm contain different amounts of mRNA and proteins.

The second way is found in mammals, where germ cells are not specified by such determinants but by signals controlled by zygotic genes. In mammals, a few cells of the early embryo are induced by signals of neighboring cells to become primordial germ cells. Mammalian eggs are somewhat symmetrical and after the first divisions of the fertilized egg, the produced cells are all totipotent. This means that they can differentiate in any cell type in the body and thus germ cells. Specification of primordial germ cells in the laboratory mouse is initiated by high levels of bone morphogenetic protein (BMP) signaling, which activates expression of the transcription factors Blimp-1/Prdm1 and Prdm14.[6]

It is speculated that induction was the ancestral mechanism, and that the preformistic, or inheritance, mechanism of germ cell establishment arose from convergent evolution.[7] There are several key differences between these two mechanisms that may provide reasoning for the evolution of germ plasm inheritance. One difference is that typically inheritance occurs almost immediately during development (around the blastoderm stage) while induction typically does not occur until gastrulation. As germ cells are quiescent and therefore not dividing, they are not susceptible to mutation.

Since the germ cell lineage is not established right away by induction, there is a higher chance for mutation to occur before the cells are specified. Mutation rate data is available that indicates a higher rate of germ line mutations in mice and humans, species which undergo induction, than in C. elegans and Drosophila melanogaster, species which undergo inheritance.[8] A lower mutation rate would be selected for, which is one possible reason for the convergent evolution of the germ plasm. However, more mutation rate data will need to be collected across several taxa, particularly data collected both before and after the specification of primordial germ cells before this hypothesis on the evolution of germ plasm can be backed by strong evidence.

Primordial germ cells, germ cells that still have to reach the gonads, also known as PGCs, precursor germ cells or gonocytes, divide repeatedly on their migratory route through the gut and into the developing gonads.[9]

In the model organism Drosophila, pole cells passively move from the posterior end of the embryo to the posterior midgut because of the infolding of the blastoderm. Then they actively move through the gut into the mesoderm. Endodermal cells differentiate and together with Wunen proteins they induce the migration through the gut. Wunen proteins are chemorepellents that lead the germ cells away from the endoderm and into the mesoderm. After splitting into two populations, the germ cells continue migrating laterally and in parallel until they reach the gonads. Columbus proteins, chemoattractants, stimulate the migration in the gonadal mesoderm.[citation needed]

In the Xenopus egg, the germ cell determinants are found in the most vegetal blastomeres. These presumptive PGCs are brought to the endoderm of the blastocoel by gastrulation. They are determined as germ cells when gastrulation is completed. Migration from the hindgut along the gut and across the dorsal mesentery then takes place. The germ cells split into two populations and move to the paired gonadal ridges. Migration starts with 3-4 cells that undergo three rounds of cell division so that about 30 PGCs arrive at the gonads. On the migratory path of the PGCs, the orientation of underlying cells and their secreted molecules such as fibronectin play an important role.[citation needed]

Mammals have a migratory path comparable to that in Xenopus. Migration begins with 50 gonocytes and about 5,000 PGCs arrive at the gonads. Proliferation occurs also during migration and lasts for 34 weeks in humans.[citation needed]

PGCs come from the epiblast and migrate subsequently into the mesoderm, the endoderm and the posterior of the yolk sac. Migration then takes place from the hindgut along the gut and across the dorsal mesentery to reach the gonads (4.5 weeks in human beings). Fibronectin maps here also a polarized network together with other molecules. The somatic cells on the path of germ cells provide them attractive, repulsive, and survival signals. But germ cells also send signals to each other.[citation needed]

In reptiles and birds, germ cells use another path. PGCs come from the epiblast and move to the hypoblast to form the germinal crescent (anterior extraembryonic structure). The gonocytes then squeeze into blood vessels and use the circulatory system for transport. They squeeze out of the vessels when they are at height of the gonadal ridges. Cell adhesion on the endothelium of the blood vessels and molecules such as chemoattractants are probably involved in helping PGCs migrate.[citation needed]

The SRY (Sex-determining Region of the Y chromosome) directs male development in mammals by inducing the somatic cells of the gonadal ridge to develop into a testis, rather than an ovary.[10]Sry is expressed in a small group of somatic cells of the gonads and influences these cells to become Sertoli cells (supporting cells in testis). Sertoli cells are responsible for sexual development along a male pathway in many ways. One of these ways involves stimulation of the arriving primordial cells to differentiate into sperm. In the absence of the Sry gene, primordial germ cells differentiate into eggs. Removing genital ridges before they start to develop into testes or ovaries results in the development of a female, independent of the carried sex chromosome.[10]

Retinoic acid (RA) is an important factor that causes differentiation of primordial germ cells. In males, the mesonephros releases retinoic acid. RA then goes to the gonad causing an enzyme called CYP26B1 to be released by sertoli cells. CYP26B1 metabolizes RA, and because sertoli cells surround primordial germ cells (PGCs), PGCs never come into contact with RA, which results in a lack of proliferation of PGCs and no meiotic entry. This keeps spermatogenesis from starting too soon. In females, the mesonephros releases RA, which enters the gonad. RA stimulates Stra8, a critical gatekeeper of meiosis (1), and Rec8, causing primordial germ cells to enter meiosis. This causes the development of oocytes that arrest in meiosis I. [11]

Gametogenesis, the development of diploid germ cells into either haploid eggs or sperm (respectively oogenesis and spermatogenesis) is different for each species but the general stages are similar. Oogenesis and spermatogenesis have many features in common, they both involve:

Despite their homologies they also have major differences:[citation needed]

After migration primordial germ cells will become oogonia in the forming gonad (ovary). The oogonia proliferate extensively by mitotic divisions, up to 5-7 million cells in humans. But then many of these oogonia die and about 50,000 remain. These cells differentiate into primary oocytes. In week 11-12 post coitus the first meiotic division begins (before birth for most mammals) and remains arrested in prophase I from a few days to many years depending on the species. It is in this period or in some cases at the beginning of sexual maturity that the primary oocytes secrete proteins to form a coat called zona pellucida and they also produce cortical granules containing enzymes and proteins needed for fertilization. Meiosis stands by because of the follicular granulosa cells that send inhibitory signals through gap junctions and the zona pellucida. Sexual maturation is the beginning of periodic ovulation. Ovulation is the regular release of one oocyte from the ovary into the reproductive tract and is preceded by follicular growth. A few follicle cells are stimulated to grow but only one oocyte is ovulated. A primordial follicle consists of an epithelial layer of follicular granulosa cells enclosing an oocyte. The pituitary gland secrete follicle-stimulating hormones (FSHs) that stimulate follicular growth and oocyte maturation. The thecal cells around each follicle secrete estrogen. This hormone stimulates the production of FSH receptors on the follicular granulosa cells and has at the same time a negative feedback on FSH secretion. This results in a competition between the follicles and only the follicle with the most FSH receptors survives and is ovulated. Meiotic division I goes on in the ovulated oocyte stimulated by luteinizing hormones (LHs) produced by the pituitary gland. FSH and LH block the gap junctions between follicle cells and the oocyte therefore inhibiting communication between them. Most follicular granulosa cells stay around the oocyte and so form the cumulus layer. Large non-mammalian oocytes accumulate egg yolk, glycogen, lipids, ribosomes, and the mRNA needed for protein synthesis during early embryonic growth. These intensive RNA biosynthese are mirrored in the structure of the chromosomes, which decondense and form lateral loops giving them a lampbrush appearance (see Lampbrush chromosome). Oocyte maturation is the following phase of oocyte development. It occurs at sexual maturity when hormones stimulate the oocyte to complete meiotic division I. The meiotic division I produces 2 cells differing in size: a small polar body and a large secondary oocyte. The secondary oocyte undergoes meiotic division II and that results in the formation of a second small polar body and a large mature egg, both being haploid cells. The polar bodies degenerate.[12] Oocyte maturation stands by at metaphase II in most vertebrates. During ovulation, the arrested secondary oocyte leaves the ovary and matures rapidly into an egg ready for fertilization. Fertilization will cause the egg to complete meiosis II. In human females there is proliferation of the oogonia in the fetus, meiosis starts then before birth and stands by at meiotic division I up to 50 years, ovulation begins at puberty.[citation needed]

A 10 - 20 m large somatic cell generally needs 24 hours to double its mass for mitosis. By this way it would take a very long time for that cell to reach the size of a mammalian egg with a diameter of 100 m (some insects have eggs of about 1,000 m or greater). Eggs have therefore special mechanisms to grow to their large size. One of these mechanisms is to have extra copies of genes: meiotic division I is paused so that the oocyte grows while it contains two diploid chromosome sets. Some species produce many extra copies of genes, such as amphibians, which may have up to 1 or 2 million copies. A complementary mechanism is partly dependent on syntheses of other cells. In amphibians, birds, and insects, yolk is made by the liver (or its equivalent) and secreted into the blood. Neighboring accessory cells in the ovary can also provide nutritive help of two types. In some invertebrates some oogonia become nurse cells. These cells are connected by cytoplasmic bridges with oocytes. The nurse cells of insects provide oocytes macromolecules such as proteins and mRNA. Follicular granulosa cells are the second type of accessory cells in the ovary in both invertebrates and vertebrates. They form a layer around the oocyte and nourish them with small molecules, no macromolecules, but eventually their smaller precursor molecules, by gap junctions.[citation needed]

The mutation frequency of female germline cells in mice is about 5-fold lower than that of somatic cells, according to one study.[13]

The mouse oocyte in the dictyate (prolonged diplotene) stage of meiosis actively repairs DNA damage, whereas DNA repair was not detected in the pre-dictyate (leptotene, zygotene and pachytene) stages of meiosis.[14] The long period of meiotic arrest at the four chromatid dictyate stage of meiosis may facilitate recombinational repair of DNA damages.[15]

Mammalian spermatogenesis is representative for most animals. In human males, spermatogenesis begins at puberty in seminiferous tubules in the testicles and go on continuously. Spermatogonia are immature germ cells. They proliferate continuously by mitotic divisions around the outer edge of the seminiferous tubules, next to the basal lamina. Some of these cells stop proliferation and differentiate into primary spermatocytes. After they proceed through the first meiotic division, two secondary spermatocytes are produced. The two secondary spermatocytes undergo the second meiotic division to form four haploid spermatids. These spermatids differentiate morphologically into sperm by nuclear condensation, ejection of the cytoplasm and formation of the acrosome and flagellum.[citation needed]

The developing male germ cells do not complete cytokinesis during spermatogenesis. Consequently, cytoplasmic bridges assure connection between the clones of differentiating daughter cells to form a syncytium. In this way the haploid cells are supplied with all the products of a complete diploid genome. Sperm that carry a Y chromosome, for example, is supplied with essential molecules that are encoded by genes on the X chromosome.[citation needed]

Success of germ cell proliferation and differentiation is also ensured by a balance between germ cell development and programmed cell death. Identification of death triggering signals and corresponding receptor proteins is important for the fertilization potential of males. Apoptosis in germ cells can be induced by variety of naturally occurring toxicant. Receptors belonging to the taste 2 family are specialized to detect bitter compounds including extremely toxic alkaloids. So taste receptors play a functional role for controlling apoptosis in male reproductive tissue. [16]

The mutation frequencies for cells throughout the different stages of spermatogenesis in mice is similar to that in female germline cells, that is 5 to 10-fold lower than the mutation frequency in somatic cells[17][13] Thus low mutation frequency is a feature of germline cells in both sexes. Homologous recombinational repair of double-strand breaks occurs in mouse during sequential stages of spermatogenesis, but is most prominent in spermatocytes.[15] The lower frequencies of mutation in germ cells compared to somatic cells appears to be due to more efficient removal of DNA damages by repair processes including homologous recombination repair during meiosis.[citation needed] Mutation frequency during spermatogenesis increases with age.[17] The mutations in spermatogenic cells of old mice include an increased prevalence of transversion mutations compared to young and middle-aged mice.[18]

Germ cell tumor is a rare cancer that can affect people at all ages. As of 2018, germ cell tumors account for 3% of all cancers in children and adolescents 0-19 years old.[19]

Germ cell tumors are generally located in the gonads but can also appear in the abdomen, pelvis, mediastinum, or brain. Germ cells migrating to the gonads may not reach that intended destination and a tumor can grow wherever they end up, but the exact cause is still unknown. These tumors can be benign or malignant.[20]

On arrival at the gonad, primordial germ cells that do not properly differentiate may produce germ cell tumors of the ovary or testis in a mouse model.[21]

Inducing differentiation of certain cells to germ cells has many applications. One implication of induced differentiation is that it may allow for the eradication of male and female factor infertility. Furthermore, it would allow same-sex couples to have biological children if sperm could be produced from female cells or if eggs could be produced from male cells. Efforts to create sperm and eggs from skin and embryonic stem cells were pioneered by Hayashi and Saitou's research group at Kyoto University.[22] These researchers produced primordial germ cell-like cells (PGLCs) from embryonic stem cells (ESCs) and skin cells in vitro.

Hayashi and Saitou's group was able to promote the differentiation of embryonic stem cells into PGCs with the use of precise timing and bone morphogenetic protein 4 (Bmp4). Upon succeeding with embryonic stem cells, the group was able to successfully promote the differentiation of induced pluripotent stem cells (iPSCs) into PGLCs. These primordial germ cell-like cells were then used to create spermatozoa and oocytes.[23]

Efforts for human cells are less advanced due to the fact that the PGCs formed by these experiments are not always viable. In fact Hayashi and Saitou's method is only one third as effective as current in vitro fertilization methods, and the produced PGCs are not always functional. Furthermore, not only are the induced PGCs not as effective as naturally occurring PGCs, but they are also less effective at erasing their epigenetic markers when they differentiate from iPSCs or ESCs to PGCs.

There are also other applications of induced differentiation of germ cells. Another study showed that culture of human embryonic stem cells in mitotically inactivated porcine ovarian fibroblasts (POF) causes differentiation into germ cells, as evidenced by gene expression analysis.[24]

Originally posted here:
Germ cell - Wikipedia

Cell Therapy Market Analysis Of Global Trends, Demand And Competition 2020-2028 – Owned

Trusted Business Insights answers what are the scenarios for growth and recovery and whether there will be any lasting structural impact from the unfolding crisis for the Cell Therapy market.

Trusted Business Insights presents an updated and Latest Study on Cell Therapy Market 2019-2026. The report contains market predictions related to market size, revenue, production, CAGR, Consumption, gross margin, price, and other substantial factors. While emphasizing the key driving and restraining forces for this market, the report also offers a complete study of the future trends and developments of the market.The report further elaborates on the micro and macroeconomic aspects including the socio-political landscape that is anticipated to shape the demand of the Cell Therapy market during the forecast period (2019-2029). It also examines the role of the leading market players involved in the industry including their corporate overview, financial summary, and SWOT analysis.

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Industry Insights, Market Size, CAGR, High-Level Analysis: Cell Therapy Market

The global cell therapy market size was valued at USD 5.8 billion in 2019 and is projected to witness a CAGR of 5.4% during the forecast period. The development of precision medicine and advancements in Advanced Therapies Medicinal Products (ATMPS) in context to their efficiency and manufacturing are expected to be the major drivers for the market. In addition, automation in adult stem cell and cord blood processing and storage are the key technological advancements that have supported the growth of the market for cell therapy. The investment in technological advancements for decentralizing manufacturing of this therapy is anticipated to significantly benefit the market. Miltenyi Biotec is one of the companies that has contributed to the decentralization in manufacturing through its CliniMACS Prodigy device. The device is an all-in-one automated manufacturing system that exhibits the capability of manufacturing various cell types.

An increase in financing and investments in the space to support the launch of new companies is expected to boost the organic revenue growth in the market for cell therapy. For instance, in July 2019, Bayer invested USD 215 million for the launch of Century Therapeutics, a U.S.-based biotechnology startup that aimed at developing therapies for solid tumors and blood cancer. Funding was further increased to USD 250 billion by a USD 35 million contribution from Versant Ventures and Fujifilm Cellular Dynamics. The biomanufacturing companies are working in collaboration with customers and other stakeholders to enhance the clinical development and commercial manufacturing of these therapies. Biomanufacturers and OEMs such as GE healthcare are providing end-to-end flexible technology solutions to accelerate the rapid launch of therapies in the market for cell therapy. The expanding stem cells arena has also triggered the entry of new players in the market for cell therapy. Celularity, Century Therapeutics, Rubius Therapeutics, ViaCyte, Fate Therapeutics, ReNeuron, Magenta Therapeutics, Frequency Therapeutics, Promethera Biosciences, and Cellular Dynamics are some startups that have begun their business in this arena lately. Use-type Insights The clinical-use segment is expected to grow lucratively during the forecast period owing to the expanding pipeline for therapies. The number of cancer cellular therapies in the pipeline rose from 753 in 2018 to 1,011 in 2019, as per Cancer Research Institute (CRI). The major application of stem cell treatment is hematopoietic stem cell transplantation for the treatment of the immune system and blood disorders for cancer patients. In Europe, blood stem cells are used for the treatment of more than 26,000 patients each year. These factors have driven the revenue for malignancies and autoimmune disorders segment. Currently, most of the stem cells used are derived from bone marrow, blood, and umbilical cord resulting in the larger revenue share in this segment. On the other hand, cell lines, such as Induced Pluripotent Stem Cells (iPSC) and human Embryonic Stem Cells (hESC) are recognized to possess high growth potential. As a result, a several research entities and companies are making significant investments in R&D pertaining to iPSC- and hESC-derived products. Therapy Type Insights of Cell Therapy Market

An inclination of physicians towards therapeutic use of autologous and allogeneic cord blood coupled with rising awareness about the use of cord cells and tissues across various therapeutic areas is driving revenue generation. Currently, the allogeneic therapies segment accounted for the largest share in 2019 in the cell therapy market. The presence of a substantial number of approved products for clinical use has led to the large revenue share of this segment.

Furthermore, the practice of autologous tissue transplantation is restricted by the limited availability of healthy tissue in the patient. Moreover, this type of tissue transplantation is not recommended for young patients wherein tissues are in the growth and development phase. Allogeneic tissue transplantation has effectively addressed the above-mentioned challenges associated with the use of autologous transplantation. However, autologous therapies are growing at the fastest growth rate owing to various advantages over allogeneic therapies, which are expected to boost adoption in this segment. Various advantages include easy availability, no need for HLA-matched donor identification, lower risk of life-threatening complications, a rare occurrence of graft failure, and low mortality rate.

Regional Insights of Cell Therapy Market

The presence of leading universities such as the Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, and Yale Stem Cell Center that support research activities in U.S. is one of the key factor driving the market for cell therapy in North America. Moreover, strong regulatory and financing support from the federal bodies for expansion of this arena in U.S. as well as Canada is driving the market. In Asia Pacific, the market is anticipated to emerge as a lucrative source of revenue owing to the availability of therapies at lower prices coupled with growing awareness among the healthcare entities and patients pertaining the potential of these therapies in chronic disease management. Japan is leading the Asian market for cell therapy, which can be attributed to its fast growth as a hub for research on regenerative medicine. Moreover, the Japan government has recognized regenerative medicine and cell therapy as a key contributor to the countrys economic growth. This has positively influenced the attention of global players towards the Asian market, thereby driving marketing operations in the region.

Market Share Insights of Cell Therapy Market

Some key companies operating in this market for cell therapy are Fibrocell Science, Inc.; JCR Pharmaceuticals Co. Ltd.; Kolon TissueGene, Inc.; PHARMICELL Co., Ltd.; Osiris Therapeutics, Inc.; MEDIPOST; Cells for Cells; NuVasive, Inc.; Stemedica Cell Technologies, Inc.; Vericel Corporation; and ANTEROGEN.CO.,LTD. These companies are collaborating with the blood centers and plasma collection centers in order to obtain cells for use in therapeutics development. Several companies have marked their presence in the market by acquiring small and emerging therapy developers. For instance, in August 2019, Bayer acquired BlueRock Therapeutics to establish its position in the market for cell therapy. BlueRock Therapeutics is a U.S. company that relies on a proprietary induced pluripotent stem cell (iPSC) platform for cell therapy development. Several companies are making an entry in the space through the Contract Development and Manufacturing Organization (CDMO) business model. For example, in April 2019, Hitachi Chemical Co. Ltd. acquired apceth Biopharma GmbH to expand its global footprint in the CDMO market for cell and gene therapy manufacturing.

Segmentations, Sub Segmentations, CAGR, & High-Level Analysis overview of Cell Therapy Market Research Report This report forecasts revenue growth at global, regional, and country levels and provides an analysis of the latest industry trends in each of the sub-segments from 2019 to 2030. For the purpose of this study, this market research report has segmented the global cell therapy market on the basis of use-type, therapy-type, and region:

Use-Type Outlook (Revenue, USD Million, 2019 2030)

Clinical-use

By Therapeutic Area

Malignancies

Musculoskeletal Disorders

Autoimmune Disorders

Dermatology

Others

By Cell Type

Stem Cell Therapies

BM, Blood, & Umbilical Cord-derived Stem Cells

Adipose derived cells

Others

Non-stem Cell Therapies

Research-use

Therapy Type Outlook (Revenue, USD Million, 2019 2030)

Allogeneic Therapies

Autologous Therapies

Quick Read Table of Contents of this Report @ Cell Therapy Market Size, Share, Market Research and Industry Forecast Report, 2020-2027 (Includes Business Impact of COVID-19)

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Cell Therapy Market Analysis Of Global Trends, Demand And Competition 2020-2028 - Owned

Embryonic Stem-Cell Research: The Promise and the Reality …

by Charles Whitaker Forerunner, "Prophecy Watch," July 2006 2006-07-01

"Know that the Lord, He is God; It is He who has made us, and not we ourselves." Psalm 100:3

Embryonic stem-cell research is both scientifically feasible and morally permissibleat least according to the majority of the electorate in the State of California. In the November 2004 elections, an overwhelming majority of those voters approved an initiative that funds embryonic stem-cell research through $3 billion worth of bonds. Emotion rather than reason probably generated most of the "aye" votes, many voters responding to the biotech industry's marketing ploy of airing testimonials from desperately sick or injured celebrities. "Don't deny us the only hope we have," they pled. "A vote against embryonic stem-cell research is a vote against life."

California's electorate asideand apparently many in both Houses of Congress, where stem-cell research bills are now being debated, as wellis the harvesting of embryonic stems cells in fact moral? Is there any substantive scientific evidence that embryonic stem-cell research can make good on its promises to cure? Who loses from this research? Who gains?

In this two-part article, we will review embryonic stem-cell research: its nature and goals, its scientific challenges, its moral issues, and its alternatives. What is it all about?

Let us start by getting the terms straight.

Embryology 101

(Underlined words are defined in the glossary at the end.)

There are two types of human reproduction: sexual and asexual. In sexual reproduction, the male gamete (or sperm cell) unites with the female gamete (or egg cell) to produce a zygote. This union is called fertilization. Half the chromosomes of the zygote come from the sperm cell, half from the egg cell.

Sexual reproduction comes in two varieties. The first, and more common, is fertilization through coition. This is in utero fertilization, where the zygote comes into being in the uterus. The second kind is in vitro fertilization (IVF), where the sperm unites with an egg in a laboratory Petri dish. From that point, the zygote (and later, the embryo) can develop in culture.

Asexual reproduction is commonly called cloning. Procedurally, the nucleus of an egg cell is removed in the laboratory. Then, the nucleus from another type of cell, any body cell, is "inserted" into that egg cell. Stimulating this egg cell with an electrical charge creates a viable zygote.

While not usually part of the syllabus of Embryology 101, it is important to understand two things about embryos.

1. First, every human zygote, no matter how it is produced, is a human being who is in his first stage of development. Every zygote is an individual. Unless death intervenes, the zygote will become an embryo, then a fetus, then an infant, then an adolescent, and eventually an adult.

2. Second, the absence of a sperm does not render an embryo created through cloning anything less than a full-fledged embryo. A cloned embryo is an embryo in every sense of the term. One writer mentions that even a stem-cell researcher as prominent as John Gearhard of Johns Hopkins University insists that the cloned organism starts out its existence as a zygote/embryo.1

Upon its creation, the zygote has two tasks immediately ahead of it. In the case of natural conception, it must implant itself into the wall of the womb. If it does not accomplish this implantation soon, it will perish for lack of nourishment. All human life, at whatever stage, must have sustenance and a proper environment to continue living.2

Embryology Development

The zygote's other task is to growto split into more cells. It starts this process almost immediately, and in the case of in utero fertilization, long before womb-attachment. Growing, the zygote becomes an embryo and later a fetus. Importantly, initial growth does not simply mean adding more cells; it does not merely imply "getting bigger." At this point, adding size, as a boy does when he "bulks up" by exercising his muscles, is not the aim in a person's development. Instead, from the single-cell zygote must spring each of the 210 basic cell types in the human body. Examples of such cell types include brain cells, bone cells, red blood cells. These are called adult cells.

Adult cells by definition perform highly specialized tasks. Red blood cells provide a good example of this specialization. Their task is to supply oxygen to other cells. They are able to carry out that task because they have iron in them. The iron oxidizes; it rusts. (That is why "red" blood cells appear red.) The oxidization process means that oxygen becomes attached to the iron. It is in fact the rusted iron, carried by these red blood cells, which provides oxygen to other cells.

The zygote's task, then, is not just to add numbers of cells, but to produce 210 different types of adult cells. The process by which a zygote does this is called cellular differentiation. Here is where embryonic stem cells enter the picture. When a zygote begins to split into other cells, it does not form specialized, adult cells. Rather, it forms stem cells. These stem cells facilitate cellular differentiation. Stem in this usage means "source" or "origin," as in the sentence, "Adultery stems from lustful thoughts." Thus, specialized (adult) cells stem from stem cells.

Cellular differentiation works this way: When a stem cell divides, it forms two cells.

One is a look-alike; it replaces the original stem cell.

The other cell is truly remarkable; it has the ability to split into something new. That something new is a differentiated stem cell, and it is quite different from the stem cell that produced it. This new stem cell is a more specialized cell, but it is not yet an adult cell.

A Stepping-Stone Process

Think of this new, different stem cell as one "stepping stone" toward the final product, an adult cell. Between original zygote and final adult cell, several stepping-stones will be needed. Each stone brings you closer to that adult cell. With each successive splitting of a stem cell, a more specialized cell comes into being, until, after a number of "generations," the adult cell appears. That cell may be, say, a red blood cellhighly specialized in its function. It could be a white blood cell, a brain cell, a bone cellany of 210 distinct types of adult cells.

What might be the basic difference between stem cells and adult cells? It is probably the type of cells they are capable of producing.

Adult cells can produce only after their kind. A white blood cell cannot breed a brain cell, but only another white blood cell.

However, the zygote and stem cells are able to produce cells quite different from themselves. The zygote is called totipotentable to generate all other cells. The earliest stem cells, those descending directly from the zygote, are also characterized by totipotency; they, too, can ultimately (that is, through several "generations" of splits) produce all other types of cellsbrain cells, bone cells, etc.

Importantly, this differentiation is not random but is tightly organized. Something signals a particular stem cell to act as the ultimate progenitor of a brain cell. That something also signals another stem cell to produce, after several generations, a liver cell. One expert summarizes the challenge this way:

Embryonic development is one of the most fascinating of all biological processes. A newly fertilized egg faces the daunting challenge of not only generating all of the tissues of the mature animal but organizing them into a functionally integrated whole. . . . If a developing embryo is not to end up a mass of disorganized tissues, it must do more than generate adult cell types. Embryos must orchestrate and choreograph an elaborate stage production that gives rise to a functional organism. They must direct intricate cell movements that bring together populations of cells only to separate them again, mold and shape organs through the birth of some cells and the death of others, and build ever more elaborate interacting systems while destroying others that serve only transient, embryonic functions. Throughout the ceaseless building, moving, and remodeling of embryonic development, new cells with unique characteristics are constantly being generated and integrated into the overall structure of the developing embryo. Science has only the most rudimentary understanding of the nature of the blueprint that orders embryonic development.3

Although not understood by man, this "blueprint that orders" is vitally important in the development of the individual. Stem cells that take ordersfollow the blueprintbuild healthy bodies. Stem cells that do not take orders result in a monster. Monster is the English translation of the Greek word teratoma, a type of tumor (benign or malignant) whose initial cells appear totipotent (or at least multipotent). They are like stem cells, keen to produce a wide variety of adult cell types (skin, bone, muscle, hair, teeth). However, the tissue they generate is "all massed together in a chaotic lump. . . . Unlike embryos, tumors generate adult cell types in a hopelessly undirected manner."4 The teratoma's initial stem-like cells lack a blueprint, or at least refuse to follow one. The result can be an often lethal, malignant monster.

Dissociated Embryonic Stem Cells

What is the nature of this ordering blueprint? Put differently: What generates the signals that tell a particular stem cell to differentiate into a red blood cell as distinct from a bone cell? How does a given stem cell know to generate a line of stem cells that will finally culminate in, say, an adult brain cell?

In this area, there are more questions than answers. Scientists know that there are three types of signals:

1. Molecular: Chemical substances are known to provide signals to embryonic stem cells.

2. Electrical: It is widely recognized that embryonic development takes place in an electrical field.

3. Mechanical: Embryonic stem cells seem to respond to structural tensions provided by cells in their proximity.

In the early 1990s, scientists learned that they could physically "extract" some stem cells from an embryo they had created through in vitro fertilization or through cloning. These separated (or "harvested") cells are called dissociated embryonic stem cells. In culture, these cells reproduce indefinitelyand fast! "One small flask of cells . . . will generate a quantity of stem cells roughly equivalent in weight to the entire human population of the earth in less than sixty days."5 However, these harvested stem cells simply reproduce; they do not differentiate into more and more specialized adult cell types. This is because they lack signals. Separated from the embryo, these dissociated cells find no blueprint to follow. They become a mass of unorganized (indeed, disorganized) cells, not unlike a teratoma.

This finding disheartened scientists until they discovered they could simulate (or replicate) those signals, or at least the chemical ones. Wow! What a blockbuster! Just provide the right signals, and there, in culture, is produced adult, disease-free cells of whatever type is needed to bring about a cure.

Let us say a scientist "signaled" these disassociated stem cells to differentiate, ultimately, into pancreatic cells, which are adult cells. Once produced in sufficient number, these adult pancreas cells could be implanted into a person with a bad pancreas, a diabetic. The effect, scientists promise, would be curative. The pancreas would eventually start producing insulin normally.

Such is the promise of embryonic stem-cell research. That is why the celebrities in California praised it so much. That is why a majority of voters added $3 billion to California's already burdensome indebtedness. The biotech firms love every minute (uh, dollar) of it!

In Search of a Better Blueprint

Bottom line, what is embryonic stem-cell research all about? Certainly, it is about determining which signal produces a pancreas cell, which produces a white blood cell, which one a bone cell, and so on. It is a search for effective signals to embryonic stem cells.

Far more fundamentally, however, it is a search for a blueprint. It is a search to find the organizing plan the zygote/embryo follows as it differentiates cells, configures them into systems, and integrates them into the single organism scientists call homo sapiens. In short, stem-cell research is the search for the pattern God uses to "fashion" us in the womb.6Psalm 139:13-16 makes it clear that God saw David's blueprint before his first stem cell split; the person David was the result of God's working "skillfully" according to that plan. David writes,

For You have formed my inward parts; You have covered me in my mother's womb. I will praise You, for I am fearfully and wonderfully made. . . . My frame was not hidden from You, When I was made in secret, And skillfully wrought in the lowest parts of the earth. Your eyes saw my substance, being yet unformed.

We can be sure that scientists, if they could figure out that blueprint, would want to make it "better." They would want to create their kind of person, a superman. Paying no attention at all to Psalm 100:3, they forget that man does not create man. God does.

Next month, we will look at the scientific challenges and moral issues that surround embryonic stem-cell research.

Glossary of Terms

Adult Cell A specialized cell, like a brain or heart cell. Unlike stem cells, an adult cell can produce cells only of its own type. Many biologists identify about 210 discreet types of adult cells.

Adult Stem Cells Stem cells present in the extra-uterine individual, retrievable by biopsy. Not to be confused with adult cells.

Cellular Differentiation The process by which stem cells generate cells quite different from themselves. The generated cells are different in that they are more specialized.

Cloning A fertilization process marked by the absence of a male gamete (sperm). The nucleus of an egg cell is removed in the laboratory. Then, the nucleus from any other body cell is "inserted" into that egg cell. Stimulating the egg cell with an electrical charge creates a zygote, which can develop in culture. The individual produced is said to be a clone of the donor who supplied the substituted nucleus.

Disassociated Embryonic Stem Cells Embryonic stem cells that are extracted from an embryo created through in vitro fertilization or through cloning. The cells so "harvested" from the embryo can be nurtured in culture, where they split indefinitely and quickly. The embryo that donates the stem cells dies.

Embryo An individual (human or animal) from the time the zygote first begins cellular differentiation. In the case of human, the organism is termed an embryo through the eighth week after fertilization.

Embryonic Stem Cells Stem cells that are the immediate descendants of the zygote. Responding to molecular, electrical, and mechanical stimuli (or signals), these cells produce more specialized stem cells, which in turn produce even more specialized stem cells. The ultimate product is an adult cell, such as a white or red blood cell.

Female Gamete Egg (ovum).

Fertilization The process by which the male gamete (sperm) unites with the female gamete (egg). The immediate result is a new individual in the zygote stage of development. Fertilization can be sexual, effected through coition or IVF, or asexual, effected through cloning.

Fetus In humans, an individual from the ninth week after fertilization until parturition (birth).

Implantation The process by which the zygote/embryo attaches itself to the womb for sustenance.

In utero Fertilization Sexual fertilization wherein the male gamete (sperm) unites with the female gamete (egg) in the uterus. This is coition, the traditional method of fertilization.

In vitro Fertilization Sexual fertilization wherein the male gamete (sperm) unites with the female gamete (egg) in a laboratory Petri dish. The embryo can then develop in culture. Acronym: IVF.

Male Gamete Sperm cell.

Multipotent Capable of differentiating into (that is, ultimately producing) a number of other types of cells, but not all types of cells, Multipotency is a characteristic of stem cells that are more than one generation away from original stem cells. Such cells are more specialized, and are less able to generate any type of cell. The more specialized a cell (that is, the more generations it is away from the original stem cells) the less multipotent it is. Also termed pluripotent.

Pre-Embryo An embryo before implantation in the womb. This term has no meaningful biological referent. "Pre-embryo" implies that the fertilized organism, before attachment to the womb, is not an embryo at all. By definition, however, the zygote became an embryo immediately after it began to split. In other words, an embryo is an embryo, regardless of its state of womb-attachment. Before attachment, an embryo is still an embryojust an un-implanted one. The term pre-embryo implies that a zygote/embryo is not a human organism until attachment and can therefore be destroyed. It is a term coined by politically-minded bio-technicians to give them "time" to kill, a window of time between fertilization and attachment. The term seeks to skirt the moral issue of murder.

Stem Cell A cell that becomes the source (hence, "stem") of other cells. Stem cells can produce more specialized cells, such as brain or bone cells. See totipotent and multipotent.

Teratoma A type of tumor resulting from multipotent (pluripotent) cells. Because the initial cells carry the characteristic of multipotency, they are similar to stem cells. However, the teratoma's cells follow no blueprint. They do not produce an organism with integrated systems, but a confused mass of tissue. In these tumors appear cell types quite different from that of the surrounding tissue (for instance, an ovarian teratoma may contain hair, teeth, and even sweat glands). Also referred to as teratomata.

Totipotent Able to differentiate into (that is, ultimately produce) all other types of cells. Totipotency is a characteristic of the zygote and of the stem cells that are its immediate progeny.

Zygote The highly specialized single cell resulting from fertilization.

Descriptive Bibliography

Campbell, Stuart, MD, Watch Me Grow! St. Martin's Press. Dr. Campbell trail-blazed the use of ultrasound. Watch Me Grow! presents a truly remarkable week-by-week window into human embryonic and fetal intrauterine development. These are not the blurry images of early ultrasound, but beautifully clear and crisp 3-D and 4-D images of younguns on their way to parturition. Watch Me Grow! is 112 pages of awe-inspiring magnificence, a remarkable use of technology to display God's glory.

Colson, Charles and Cameron, Nigel, eds., Human Dignity in the Biotech Century: A Christian Vision for Public Policy, InterVarsity Press. This collection of surveys by experts covers every facet of modern biotechnology: IVF, cloning, stem-cell research, genetic engineering. Eric Cohen, editor of the New Atlantis, reviews this book in the January 2005 number of First Things (http://www.firstthings.com/ftissues/ft0501/reviews/cohen.htm).

Condic, L. Maureen, "The Basic Facts about Stem Cells," First Things, January 2002, p. 30. This short article provides the "must know" facts about stem-cell research. This article is available at http://www.firstthings.com/ftissues/ft0201/articles/condic.html.

Condic, "Stem Cells and False Hopes," First Things, August/September 2002, p. 20. Ms. Condic, Assistant Professor of Neurobiology and Anatomy at the University of Utah, discusses the exploitation of desperately sick individuals by biotech firms. This article is available at http://www.firstthings.com/ftissues/ft0208/opinion/condic.html.

Saunders, Jr., William L., "Embryology: Inconvenient Facts," First Things, December 2004, p. 15. Saunders, Senior Fellow and Director of the Center for Human Life and Bioethics, presents authoritative arguments for the nature of zygote and embryo, and shows how modern bio-technicians hide meaning behind verbal sophistries. This article is available at http://www.firstthings.com/ftissues/ft0412/opinion/saunders.htm

National Catholic Bioethics Quarterly. This big journal (each issue is over 200 pages) is published by the National Catholic Bioethics Center in Boston. Because of the obvious Catholic focus, members of God's church will find many articles off base, yet this journal remains one of the best single sources of reasoned information on the subjects of bioethics and biotechnology. Some articles are quite technical. For more information, write the National Catholic Bioethics Quarterly, PO Box 3000, Denville, NJ 07834-9772 ($48/year).

Endnotes

1 Saunders, Jr., William L, "Embryology: Inconvenient Facts," First Things, December 2004, p. 15. 2 After the mid-1980s, bio-technicians spoke of a pre-embryo as an organism before womb-attachment. The implication is that the pre-embryo is non-human; the implanted embryo human. This false concept will be discussed more fully in Part Two. Suffice it to say that there is really no such thing as a pre-embryo. An embryo is an embryo. An unattached one is an embryo in every sense of the definition. It is just unattached. 3 Condic, Maureen, "The Basics about Stem Cells," First Things, January 2002, p 30. 4 Ibid. 5 Ibid. 6 See Psalm 119:73.

Original post:
Embryonic Stem-Cell Research: The Promise and the Reality ...

Chaperone-mediated autophagy regulates the pluripotency of …

Autophagy regulates stemness

Embryonic stem cells can propagate indefinitely and differentiate when called to do so. Xu et al. now analyze how cellular metabolism affects the balance between pluripotency and differentiation (see the Perspective by Borsa and Simon). For cells in the pluripotent state, the transcription factors Oct4 and Sox2 suppress chaperone-mediated autophagy (CMA). When CMA is released with differentiation, the isocitrate dehydrogenases IDH1 and IDH2 are degraded, resulting in less -ketoglutarate, which is needed by the histone and DNA demethylases that sustain pluripotency. CMA thus links cellular metabolism to epigenetic regulation, tipping the balance between pluripotent renewal and differentiation.

Science, this issue p. 397; see also p. 373

Embryonic stem cells can propagate indefinitely in a pluripotent state, able to differentiate into all types of specialized cells when restored to the embryo. What sustains their pluripotency during propagation remains unclear. Here, we show that core pluripotency factors OCT4 and SOX2 suppress chaperone-mediated autophagy (CMA), a selective form of autophagy, until the initiation of differentiation. Low CMA activity promotes embryonic stem cell self-renewal, whereas its up-regulation enhances differentiation. CMA degrades isocitrate dehydrogenases IDH1 and IDH2 and reduces levels of intracellular -ketoglutarate, an obligatory cofactor for various histone and DNA demethylases involved in pluripotency. These findings suggest that CMA mediates the effect of core pluripotency factors on metabolism, shaping the epigenetic landscape of stem cells and governing the balance between self-renewal and differentiation.

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Chaperone-mediated autophagy regulates the pluripotency of ...

Genetic puzzle: How mice can be modified to help in the race to develop coronavirus therapies – Genetic Literacy Project

For more than three decadesMichael Koob has been working out complicated puzzles using the tools of molecular biology and genetics. Today his deliberative labors are paying offwith untold implications for the study of human disease and the development of drug therapies and vaccines. Koob has figured out how to replace entire genes of laboratory mice with their human counterparts, transporting huge segments of human DNA to their proper corresponding location in mouse chromosomes. Now he is applying his genetic puzzle-solving ingenuity to the scourge of the COVID-19 pandemic.

An LMP associate professor, Koob launched his molecular investigations while a graduate student at the University of Wisconsin in Madison, where he earned a PhD in molecular and cellular biology in 1990. His graduate adviser was the legendary molecular geneticist Waclaw Szybalski. Koob and Szybalski pioneered a technique they called Achilles heel cleavage that cuts DNA in a single targeted location, which enabled them to create large DNA segments. Koob joined the LMP faculty in 1995. He brought with him those early insights about how to use molecular tools to manipulate DNA in human and animal cells and thereby answer questions about health and disease.

Now Koob has set his sights onCOVID-19, the disease caused by coronavirusSARS-CoV-2 infection. SARS-CoV-2 respiratory viruses enter human lung tissue via a cell-surface receptor molecule called angiotensin-converting enzyme 2 orACE2. Once in the lung the virus multiplies and travels throughout the organ, in some patients causing Acute Respiratory Distress Syndrome (ARDS), which can be fatal.

But theres a problem in using mice to understand SARS-CoV-2 infection and COVID-19 disease progression. In the mouse, the ACE2 receptor doesnt bind the virus, so mice dont get infected and show the respiratory symptoms we see in people, Koob said. But what if mice expressed the human gene for the ACE2 receptor instead of their own? That would potentially enable investigators to track COVID-19 pathology beginning with infection and viral replication in airway epithelial cells all the way to lower lung zones where the virus often settles, consolidates, and can cause viral pneumonia. That mouse model is under construction in Koobs laboratory.

Infection at the entry point would make the mouse model work for COVID-19, and full human ACE2 receptor gene substitution for the mouse version should make infection possible, Koob said. The internal viral replication will be maintained between the mouse and humans. So this should model the infection route, disease progression in the lungs, everything like that. Its really just basic cell biology. If you want to mimic what happens in a person the most important thing really is to get the cell types correct. If the right cells are ACE2 receptor-positive, then you can mimic what happens in people.

Other research groups have transferred only a small part of the ACE2 receptor DNA gene sequence into mice, creating transgenic animals but ones that do not mimic the potentially lethal lung pathology of a SARS-CoV-2 infection and COVID-19, such as ARDS. Koobs team will replace the entire mouse ACE2 receptor gene with the entire human ACE2 receptor gene plus associate regulatory sequencestransferring in all some 70,000 DNA sequences to the precise location on the mouse chromosome where its own ACE2 receptor gene once resided. The mouse gene will be gone, and the human gene will be there, Koob said. It now becomes a human ACE2 receptor gene in a true sense. The sequence of tissues that become positive for ACE2 receptor expression should be recapitulated.

When a human gene is put in the same spot where the mouse gene once resided, genomic regulatory factors come into play that are appropriate for that gene, Koob said. Theres a global regulatory context to take into account in animals that have a common ancestor, which all mammals do. Mice and humans arefairly close on the evolutionary tree. So theres global regulation if we put it in the right spot. The right spot transfer of the human gene construct is into a mouse embryonic stem cell, which Koob then puts into a blastocyst or early mouse embryo. Selective breeding yields mice with the human gene in all cells and tissues.

Related article: Viewpoint: Coronavirus pandemic accelerates progress toward tech-driven, sustainable food system

A search of the databaseClinicalTrials.govyields more than 400 studies when the terms COVID-19 and lung therapy are combined. Small molecule drugs, therapeutic antibodies and antivirals, immunotherapies, stem cells and natural killer cells, steroids, and laser and radiotherapies are among the lung injury therapies currently being investigated. A validated, reliable, and clinically informative mouse model for testing COVID-19 lung injury therapies would be invaluable, as it would be for future coronavirus vaccine trials.

Koob anticipates his human ACE2 receptor gene mouse strain will be ready by this fall. He will send it by courier toJackson Laboratory(JAX) in Bar Harbor, Maine to join more than 11,000 strains of mice that JAX distributes to researchers around the world. JAX will breed the mice over several months while Koob and LMP professorsSteve JamesonandKris Hogquistand Department of Medicine assistant professorTyler Bold, all at the Center for Immunology, conduct characterization and SARS-CoV-2 infection studies of the mice in aLevel 3 biosafetyfacility. JAX is currently distributingKoobs full gene replacement mouse strainthat carries the human microtubule-associated proteintau, which is responsible for the neurofibrillary tangles in the brain associated with Alzheimers disease and other dementias. Koob is making full gene replacement mouse models of other neurodegenerative diseases.

Our philosophy is to make our mouse strains available to the research community in an expedited way, Koob said. I contacted JAX about this ACE2 receptor gene replacement mouse. Theyre very happy to collaborate with us because they dont have anything like this. And were making it available to researchers without restrictions.

With Koob and his laboratory scientist Kellie Benzow as inventors, the University has filed a patent onMethods of full gene replacement and transgenic non-human cells comprising full human genes.

Its been a long time since Koob collaborated with his graduate adviser Waclaw Szybalski, now a 98-year-old professor emeritus. Together their research careers encompass the history of molecular biology going back to the early 1950s with the discovery of the DNA double helix. Szybalski was born in 1921 just after a pandemic virus infected an estimated one-third of the Earths population and killed tens of millions of people. A century later, with another pandemic raging, the timing couldnt be better for his student to exercise his manifest molecular inventiveness.

William Hoffman is a writer and editor at the University of Minnesota. He has worked closely with faculty in genetics and bioengineering, medical technology and bioscience industries, and the science policy and ethics communities. He is author with Leo Furcht of Divergence, Convergence, and Innovation: East-West Bioscience in an Anxious Age, Asian Biotechnology and Development Review, Nov. 2014.

A version of this article was originally published at the University of Minnesota website and has been republished here with permission. The University of Minnesota can be found on Twitter @UMNews

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Genetic puzzle: How mice can be modified to help in the race to develop coronavirus therapies - Genetic Literacy Project