Category Archives: Embryonic Stem Cells

Growing Organs in the Lab: One Step Closer to Reality – BioSpace

Researchers these days routinely use pluripotent stem cells to develop into specific tissue cells, and a variety of methods to coax those tissues to grow in Petri dishes into simple organoids. The goal, in many cases, is to grow realistic, complex organs that are not only excellent models for research but have the possibility of use for full-blown organ transplants. For example, in April 2019, researchers at Tel Aviv University successfully bioprinted the first 3D human heart using the patients own cells and various biological materials such as collagen and glycoprotein.

Now this has moved a step further. To date, these grown or bioprinted organoids are incomplete, lacking some of the vasculature and infrastructure of organs. But researchers at the University of Wrzburg in Germany took their research one step further.

We used a trick to achieve our goal, said Philipp Wrsdrfer with the Institute of Anatomy and Cell Biology at Wrzburg. First we created so-called mesodermal progenitor cells from pluripotent stem cells.

Under specific conditions, these progenitor cells can produce blood vessels, immune cells and connective tissue cells. The researchers mixed the progenitor cells with cancer cells as well as brain stem cells that had earlier been developed from human iPS cells.

The mixture of cells grew and formed complex three-dimensional tumor or brain organoids in a petri dish. The organoids had functional blood vessels and connective tissue. In the brain tissue, microglia cells were developed, which are brain-specific immune cells.

The research was published in the journal Scientific Reports.

In the future, the miniature organ models generated with this new technique can help scientists shed light on the processes involved in the genesis of diseases and analyze the effect of therapeutic substances in more detail using them on animals and human patients, said Sleyman Ergn, who conducted the work with Wrsdrfer. This would allow the number of animal experiments to be reduced. Moreover, the organ models could contribute to gaining a better understanding of embryonic development processes and grow tissue that can be transplanted efficiently since they already have a functional vascular system.

The authors wrote, Organoids derived from human induced pluripotent stem cells (hiPSCs) are state of the art cell culture models to study mechanisms of development and disease. The establishment of different tissue models such as intestinal, liver, cerebral, kidney and lung organoids was published within the last years. These organoids recapitulate the development of epithelial structures in a fascinating manner. However, they remain incomplete as vasculature, stromal components and tissue resident immune cells are mostly lacking.

About a year ago, researchers at Johns Hopkins University, the University of California, San Diego (UCSD) and the National Institute of Mental Health grew retinas in Petri dishes. The retina is the part of the eye that collects light and translates it into the signals that the brain interprets as vision. The cells grew into 20 to 60 tiny balls of cells, called retinal organoids. The tiny human retinas responded to light and were used in their research to better understand how color vision develops.

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Growing Organs in the Lab: One Step Closer to Reality - BioSpace

Major step taken in creating complex organs in the lab – Drug Target Review

A major step has been taken towards developing functional miniature versions of human organs in a Petri dish which can be used to shed light on the processes involved in the genesis of diseases.

Scientists from the University of Wrzburg, Germany have taken a major step towards developing functional miniature versions of human organs, known as complex organoids.

Japanese researchers had previously developed a way of creating pluripotent stem cells through epigenetic reprogramming of connective tissue cells, which has yielded a highly valuable cell type that can be used to grow all cells of the human body in a Petri dish.

When culturing these so-called induced pluripotent stem cells (iPS cells) as three-dimensional (3D) cell aggregates, the organoids can be created by selectively adding growth factors.

Such organoid models are often similar to real embryonic tissues. However, most remained incomplete because they lacked stromal cells and structures, the supportive framework of an organ composed of connective tissue.

This new development was part of a project led by Dr Philipp Wrsdrfer and Professor Sleyman Ergn, the head of the Institute of Anatomy and Cell Biology, which has resulted in organoids that have complexity similar to that of normal tissue and are far superior to previous structures.

Organoid models are often surprisingly similar to real embryonic tissues. Shown here (from left): 3D reconstruction of the vascular network within an organoid, brain organoid with blood vessels (red) and brain stem cells (green) and a tumour organoid with blood vessels (red) and tumour cells (green) (credit: Institute for Anatomy and Cell Biology).

We used a trick to achieve our goal, explained Philipp Wrsdrfer. First we created so-called mesodermal progenitor cells from pluripotent stem cells. Under the right conditions, such progenitor cells are capable of producing blood vessels, immune cells and connective tissue cells.

To demonstrate the potential of the mesodermal progenitor cells, the scientists mixed these cells with tumour cells and brain stem cells that had previously been generated from human iPS cells. This mixture grew to form complex 3D tumour or brain organoids in the Petri dish featuring functional blood vessels, connective tissue, and in the case of the brain tissue, brain-specific immune cells.

In the future, the miniature organ models generated with this new technique can help scientists shed light on the processes involved in the genesis of diseases and to analyse the effect of therapeutic substances in more detail before using them on animals and human patients, added Sleyman Ergn.

This would allow the number of animal experiments to be reduced. Moreover, the organ models could contribute to gaining a better understanding of embryonic development processes and grow tissue that can be transplanted efficiently.

The project was published Scientific Reports.

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Major step taken in creating complex organs in the lab - Drug Target Review

Cell Therapy Aims To Improve Memory and Prevent Seizures Following Traumatic Brain Injury – Technology Networks

Researchers from the University of California, Irvine developed a breakthrough cell therapy to improve memory and prevent seizures in mice following traumatic brain injury. The study, titled Transplanted interneurons improve memory precision after traumatic brain injury, was published today inNature Communications.

Traumatic brain injuries affect 2 million Americans each year and cause cell death and inflammation in the brain. People who experience a head injury often suffer from lifelong memory loss and can develop epilepsy.

In the study, the UCI team transplanted embryonic progenitor cells capable of generating inhibitory interneurons, a specific type of nerve cell that controls the activity of brain circuits, into the brains of mice with traumatic brain injury. They targeted the hippocampus, a brain region responsible for learning and memory.

The researchers discovered that the transplanted neurons migrated into the injury where they formed new connections with the injured brain cells and thrived long term. Within a month after treatment, the mice showed signs of memory improvement, such as being able to tell the difference between a box where they had an unpleasant experience from one where they did not. They were able to do this just as well as mice that never had a brain injury. The cell transplants also prevented the mice from developing epilepsy, which affected more than half of the mice who were not treated with new interneurons.

Inhibitory neurons are critically involved in many aspects of memory, and they are extremely vulnerable to dying after a brain injury, saidRobert Hunt, PhD, assistant professor of anatomy and neurobiology at UCI School of Medicine who led the study. While we cannot stop interneurons from dying, it was exciting to find that we can replace them and rebuild their circuits.

This is not the first time Hunt and his team has used interneuron transplantation therapy to restore memory in mice. In 2018, the UCI team used asimilar approach, delivered the same way but to newborn mice, to improve memory of mice with a genetic disorder.

Still, this was an exciting advance for the researchers. The idea to regrow neurons that die off after a brain injury is something that neuroscientists have been trying to do for a long time, Hunt said. But often, the transplanted cells dont survive, or they arent able to migrate or develop into functional neurons.

To further test their observations, Hunt and his team silenced the transplanted neurons with a drug, which caused the memory problems to return.

"It was exciting to see the animals memory problems come back after we silenced the transplanted cells, because it showed that the new neurons really were the reason for the memory improvement, said Bingyao Zhu, a junior specialist and first author of the study.

Currently, there are no treatments for people who experience a head injury. If the results in mice can be replicated in humans, it could have a tremendous impact for patients. The next step is to create interneurons from human stem cells.

So far, nobody has been able to convincingly create the same types of interneurons from human pluripotent stem cells, Hunt said. But I think were close to being able to do this.

Jisu Eom, an undergraduate researcher, also contributed to this study. Funding was provided by the National Institutes of Health.

Reference: Zhu, et al. (2019) Transplanted interneurons improve memory precision after traumatic brain injury. Nature Communications. DOI:https://doi.org/10.1038/s41467-019-13170-w

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Cell Therapy Aims To Improve Memory and Prevent Seizures Following Traumatic Brain Injury - Technology Networks

WCM-Q explores law and ethics of stem cells and AI in medicine – The Peninsula Qatar

18 Nov 2019 - 8:02

Speakers at WCM-Qs Law and Medicine event taking part in a panel discussion on the law and ethics of stem cell science.

The legal and ethical implications of using stem cells and artificial intelligence (AI) in medicine were discussed at the latest instalment of Weill Cornell Medicine-Qatars (WCM-Q) Intersection of Law & Medicine series.Expert speakers at the event discussed the impact of recent advances in stem cell science and AI on the practice of medicine in Qatar and explored how new legal frameworks could be developed to protect the rights and safety of patients in the MENA region. The day-long event was organized by WCM-Q in collaboration with Hamad Bin Khalifa University and the University of Malaya of Kuala Lumpur, Malaysia.Stem cells are an exciting area for medical researchers because they have the potential to repair damaged or diseased tissues in people with conditions such as Parkinsons disease, type 1 diabetes, stroke, cancer, and Alzheimers disease, among many others. Stem cells can also be used by researchers to test new drugs for safety and effectiveness.WCM-Qs Dr. Amal Robay, WCM-Q assistant professor in genetic medicine and director of research compliance, said: Stem cells have the capacity for unlimited or prolonged self-renewal, and they can differentiate themselves into many different cell types to become tissue- or organ-specific cells with special functions. The central ethical dilemma of stem cell science arises from the fact that embryonic stem cells are derived from human embryos or by cloning, she explained.Visiting bioethics expert Dr. Jeremy Sugarman of Johns Hopkins University in Baltimore, US said that the public image of stem cell research had been damaged by a small number of high-profile cases in which scientists had behaved unethically. The field had also been hampered by different countries applying different laws to stem cell research, making international collaboration problematic, he said.Meanwhile, the use of AI in healthcare has the potential to leverage analysis of large amounts of data to improve patient outcomes, but poses ethical concerns regarding privacy, the diversity of data sources, biases and relying on non-human entities for potentially life-changing decisions.Dr. Barry Solaiman, assistant professor of law in the College of Law and Public Policy at HBKU said: Its very important that we bridge that gap between the professions of law and medicine, and that we understand the fundamental importance of ethicists to the advance of science. We need to consider how lawyers can help to develop laws to ensure that science advances and that it does so in ways that protect everyone involved.The event, which was co-directed by Dr. Solaiman and Dr. Thurayya Arayssi, professor of clinical medicine and senior associate dean for medical education and continuing professional development at WCM-Q, also featured other expert speakers.The event was accredited locally by the Qatar Council for Healthcare Practitioners-Accreditation Department (QCHP-AD) and internationally by the Accreditation Council for Continuing Medical Education (ACCME).

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WCM-Q explores law and ethics of stem cells and AI in medicine - The Peninsula Qatar

Qatar- WCM-Q explores law and ethics of stem cells and AI in medicine – MENAFN.COM

(MENAFN - The Peninsula) The legal and ethical implications of using stem cells and artificial intelligence (AI) in medicine were discussed at the latest instalment of Weill Cornell Medicine-Qatar's (WCM-Q) Intersection of Law & Medicine series.Expert speakers at the event discussed the impact of recent advances in stem cell science and AI on the practice of medicine in Qatar and explored how new legal frameworks could be developed to protect the rights and safety of patients in the MENA region. The day-long event was organized by WCM-Q in collaboration with Hamad Bin Khalifa University and the University of Malaya of Kuala Lumpur, Malaysia.Stem cells are an exciting area for medical researchers because they have the potential to repair damaged or diseased tissues in people with conditions such as Parkinson's disease, type 1 diabetes, stroke, cancer, and Alzheimer's disease, among many others. Stem cells can also be used by researchers to test new drugs for safety and effectiveness.WCM-Q's Dr. Amal Robay, WCM-Q assistant professor in genetic medicine and director of research compliance, said: 'Stem cells have the capacity for unlimited or prolonged self-renewal, and they can differentiate themselves into many different cell types to become tissue- or organ-specific cells with special functions. The central ethical dilemma of stem cell science arises from the fact that embryonic stem cells are derived from human embryos or by cloning, she explained.Visiting bioethics expert Dr. Jeremy Sugarman of Johns Hopkins University in Baltimore, US said that the public image of stem cell research had been damaged by a small number of high-profile cases in which scientists had behaved unethically. The field had also been hampered by different countries applying different laws to stem cell research, making international collaboration problematic, he said.Meanwhile, the use of AI in healthcare has the potential to leverage analysis of large amounts of data to improve patient outcomes, but poses ethical concerns regarding privacy, the diversity of data sources, biases and relying on non-human entities for potentially life-changing decisions.Dr. Barry Solaiman, assistant professor of law in the College of Law and Public Policy at HBKU said: 'It's very important that we bridge that gap between the professions of law and medicine, and that we understand the fundamental importance of ethicists to the advance of science. We need to consider how lawyers can help to develop laws to ensure that science advances and that it does so in ways that protect everyone involved.The event, which was co-directed by Dr. Solaiman and Dr. Thurayya Arayssi, professor of clinical medicine and senior associate dean for medical education and continuing professional development at WCM-Q, also featured other expert speakers.The event was accredited locally by the Qatar Council for Healthcare Practitioners-Accreditation Department (QCHP-AD) and internationally by the Accreditation Council for Continuing Medical Education (ACCME).

MENAFN1811201900630000ID1099287087

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Qatar- WCM-Q explores law and ethics of stem cells and AI in medicine - MENAFN.COM

New cell therapy improves memory and stops seizures after brain injury – Drug Target Review

A recent study has shown that transplanting new inhibitory neurons may repair damaged brain circuits.

A breakthrough cell therapy to improve memory and prevent seizures in mice following traumatic brain injury (TBI) has been developed by researchers.

In the study, the research team from the University of California, US transplanted embryonic progenitor cells capable of generating inhibitory interneurons (a specific type of nerve cell that controls the activity of brain circuits) into the brains of mice with traumatic brain injury, targeting the hippocampus.

These are transplanted inhibitory neurons (green) successfully incorporated into the hippocampus of a mouse with traumatic brain injury (credit: UCI School of Medicine).

The researchers discovered that the transplanted neurons migrated into the injury where they formed new connections with the injured brain cells and thrived long term. Within a month after the treatment, the mice models showed signs of memory improvement.

The cell transplants also prevented the mice from developing epilepsy, which affected more than half of the mice who were not treated with new interneurons.

Inhibitory neurons are critically involved in many aspects of memory, and they are extremely vulnerable to dying after a brain injury, said Robert Hunt, PhD, assistant professor of anatomy and neurobiology at UCI School of Medicine who led the study. While we cannot stop interneurons from dying, it was exciting to find that we can replace them and rebuild their circuits.

To further test their observations, the team silenced the transplanted neurons with a drug, which caused the memory problems to return.

It was exciting to see the animals memory problems come back after we silenced the transplanted cells, because it showed that the new neurons really were the reason for the memory improvement, added Bingyao Zhu, a junior specialist and first author of the study.

So far, nobody has been able to convincingly create the same types of interneurons from human pluripotent stem cells, Hunt concluded. But I think were close to being able to do this.

The study was published in Nature Communications.

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New cell therapy improves memory and stops seizures after brain injury - Drug Target Review

Stem Cell Therapy Market by Treatment,Application,End Users and Geography Forecast To 2026 – Markets Gazette 24

Stem Cell Therapy Market is expected to reach 202.77 billion by 2026 from 12.25 billion in 2017 at CAGR of 42.02%.(Detailed analysis of the market CAGR is provided in the report) stands for use of stem cells to treat or prevent disease or condition.

Bone marrow transplant and some therapies derived from umbilical cord blood are mainly used in stem cell therapy. Advancement, in order to establish new sources for stem cells, and to apply stem-cell treatments for neurodegenerative diseases and conditions such as diabetes, heart disease, and other conditions, are increased in recent years. Stem Cell Therapy Market Researchers are making efforts to discover novel methods to create human stem cells. This will increase the demand as well as supply for stem cell production and potential investigation in disease management. Increasing investment & research grants for developing safe and effective stem cell therapy products, the growing patient base for target diseases, concentrated product pipelines, increasing approval of the new clinical trials, rapid technological advancement in genomics, and the rising awareness about the stem cell are expected to drive the growth of the Stem Cell Therapy solutions market during the forecast period.

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However, improper infrastructure, insufficient storage systems, nascent technology in underdeveloped economies, Ethical issues related to an embryonic stem cell, low patient acceptance rate, Difficulty in the preservation of stem cell are expected to restrain the market growth. North America is expected to be the largest growing region by 2026; the reason behind that is extensive funding by Government. However, Emerging countries like India, china, Korea have low growth rate as compared to Developed regions in 2017 but increase in awareness about stem cell therapy will lead the Asia Pacific to generate a significant level of revenue by 2026.

Key Highlights of Stem Cell Therapy Market report

Detailed quantitative analysis of the current and future trends from 2017 to 2026, which helps to identify the prevailing market opportunities.Comprehensive analysis of factors instrumental in changing the market scenario, rising prospective opportunities, market shares, core competencies in terms of market development, growth strategies and identification of key companies that can influence this market on a global and regional scale.Assessment of Market definition along with the identification of key drivers, restraints opportunities and challenges for this market during the forecast period.Complete analysis of micro-markets with respect to individual growth trends, prospects, and contributions to the overall Stem Cell Therapy Solutions market.Stem Cell Therapy market analysis and comprehensive segmentation with respect to the Application, End users, Treatment, and geography to assist in strategic business planning.Stem Cell Therapy market analysis and forecast for five major geographies-North America, Europe, Asia Pacific, Middle East & Africa, Latin America, and their key regions.For company profiles, 2017 has been considered as the base year. In cases, wherein information was unavailable for the base year, the years prior to it have been considered.

Research Methodology:

The market is estimated by triangulation of data points obtained from various sources and feeding them into a simulation model created individually for each market. The data points are obtained from paid and unpaid sources along with paid primary interviews with key opinion leaders (KOLs) in the market. KOLs from both, demand and supply side were considered while conducting interviews to get an unbiased idea of the market. This exercise was done at a country level to get a fair idea of the market in countries considered for this study. Later this country-specific data was accumulated to come up with regional numbers and then arrive at a global market value for the stem cell therapy market.

Key Players in the Stem Cell Therapy Market are:

Chiesi Farmaceutici S.P.A Are:Gamida CellReNeuron Group, plcOsiris Therapeutics, Inc.Stem Cells, Inc.Vericel Corporation.Mesoblast, Ltd.

Key Target Audience:

Stem Cell Associations and OrganizationsGovernment Research Boards and OrganizationsResearch and consulting firmsStem Cell Therapy Market InvestorsHealthcare Service Providers (including Hospitals and Diagnostic Centers)Stem Cell Therapeutic Product Manufacturing OrganizationsResearch LabsClinical research organizations (CROs)Stem Cell Therapy Marketing PlayersPharmaceutical Product Manufacturing Companies

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Scope of the Stem Cell Therapy Market Report:

Stem Cell Therapy market research report categorizes the Stem Cell Therapy market based on Application, End users, Treatment, and geography (region wise). Market size by value is estimated and forecasted with the revenues of leading companies operating in the Stem Cell Therapy market with key developments in companies and market trends.

Stem Cell Therapy Market, By Treatments:

Allogeneic Stem Cell TherapyAutologous Stem Cell Therapy

Stem Cell Therapy Market, By End Users:

HospitalsAmbulatory Surgical Centers

Stem Cell Therapy Market, By Application:

OncologyCentral Nervous System DiseasesEye DiseasesMusculoskeletal DiseasesWound & InjuriesMetabolic DisordersCardiovascular DisordersImmune System Disorders

Stem Cell Therapy Market, By Geography:

North AmericaEuropeAsia PacificMiddle East & AfricaLatin America

Available Customization:

With the given market data, Maximize Market Research offers customization of report and scope of the report as per the requirement

Regional Analysis:

Breakdown of the North America stem cell therapy marketBreakdown of the Europe stem cell therapy marketBreakdown of the Asia Pacific stem cell therapy marketBreakdown of the Middle East & Africa stem cell therapy marketBreakdown of the Latin America stem cell therapy market

Company Information:Detailed analysis and profiles of addition

Browse Full Report with Facts and Figures of Stem Cell Therapy Market Report at: https://www.maximizemarketresearch.com/market-report/stem-cell-therapy-market/522/

MAJOR TOC OF THE REPORT

Chapter One: Stem Cell Therapy Market Overview

Chapter Two: Manufacturers Profiles

Chapter Three: Global Stem Cell Therapy Market Competition, by Players

Chapter Four: Global Stem Cell Therapy Market Size by Regions

Chapter Five: North America Stem Cell Therapy Revenue by Countries

Chapter Six: Europe Stem Cell Therapy Revenue by Countries

Chapter Seven: Asia-Pacific Stem Cell Therapy Revenue by Countries

Chapter Eight: South America Stem Cell Therapy Revenue by Countries

Chapter Nine: Middle East and Africa Revenue Stem Cell Therapy by Countries

Chapter Ten: Global Stem Cell Therapy Market Segment by Type

Chapter Eleven: Global Stem Cell Therapy Market Segment by Application

Chapter Twelve: Global Stem Cell Therapy Market Size Forecast (2019-2026)

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Stem Cell Therapy Market by Treatment,Application,End Users and Geography Forecast To 2026 - Markets Gazette 24

Global Stem Cell Assay Market 2019 Size, Share, Growth, Trends, Type, Application, Analysis and Forecast by 2026 – Markets Gazette 24

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Highlights of the report:A complete backdrop analysis, which includes an assessment of the parent market. Important changes in market dynamics market segmentation up to the second or third level. Historical, current, and projected size of the market from the standpoint of both value and volume. Reporting and evaluation of recent industry developments market shares and strategies of key players. Emerging niche segments and regional markets. Objective assessment of the trajectory of the market. Recommendations to companies for strengthening their foothold in the market

On the basis of type, the market is split into:* Viability/Cytotoxicity* Isolation & Purification* Cell Identification* Proliferation* Differentiation* Function* Apoptosis

On the basis of cell type, the market is split into:* Human embryonic stem cells (hESCs)* Adult Stem Cells

On the basis of product & service, the market is split into:* Instruments* Kits* Services

The key players profiled in the market include:* Thermo Fisher Scientific* Merck KGaA* GE Healthcare* Bio-Rad Laboratories* Promega Corporation* Agilent Technologies* Perkinelmer

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Key Benefits of the Report:

* Global, regional, type, cell type, product & service, application, end user market size and their forecast from 2015-2026

* Identification and detailed analysis on key market dynamics, such as, drivers, restraints, opportunities, and challenges influencing growth of the market

* Detailed analysis on industry outlook with market specific PESTLE, and supply chain to better understand the market and build expansion strategies

* Identification of key market players and comprehensively analyze their market share and core competencies, detailed financial positions, key products, and unique selling points

* Analysis on key players strategic initiatives and competitive developments, such as joint ventures, mergers, and new product launches in the market

* Expert interviews and their insights on market shift, current and future outlook, and factors impacting vendors short term and long term strategies

* Detailed insights on emerging regions, type, cell type, product & service, application, end user with qualitative and quantitative information and facts

Target Audience:

* Stem Cell Assay Product Manufacturers

* Traders, Importers, and Exporters

* Raw Material Suppliers and Distributors

* Government and Research Organizations

* Associations and Industry Bodies

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Research Methodology:

The market is derived through extensive use of secondary, primary, in-house research followed by expert validation and third party perspective, such as, analyst reports of investment banks. The secondary research is the primary base of our study wherein we conducted extensive data mining, referring to verified data sources, such as, white papers, government and regulatory published articles, technical journals, trade magazines, and paid data sources.

For forecasting, regional demand & supply factors, recent investments, market dynamics including technical growth scenario, consumer behavior, and end use trends and dynamics, and production capacity were taken into consideration. Different weightages have been assigned to these parameters and quantified their market impacts using the weighted average analysis to derive the market growth rate.

The market estimates and forecasts have been verified through exhaustive primary research with the Key Industry Participants (KIPs), which typically include:

* Manufacturers

* Suppliers

* Distributors

* Government Body & Associations

* Research Institutes

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Global Stem Cell Assay Market 2019 Size, Share, Growth, Trends, Type, Application, Analysis and Forecast by 2026 - Markets Gazette 24

Oct4, Considered Vital for Creating iPSCs, Actually Isnt Needed – The Scientist

Since 2006, when Shinya Yamanaka, now the director of the Center for iPS Cell Research and Application at Kyoto University, discovered a method that could guide fully differentiated cells back to their pluripotent state, scientist have been using his recipe to produce induced pluripotent stem cells. The protocol relies on overexpressing the so-called Yamanaka factors, which are four transcription factors: Oct4, Sox2, Klf4, and cMyc (OSKM). While the technique reliably creates iPS cells, it can cause unintended effects, some of which can lead to cells to become cancerous. So researchers have worked to adjust the cocktail and understand the function of each factor.

No one had succeeded in creating iPS cells without forcing the overexpression of Oct4. It was thought that this was the most crucial factor of the four. At least until now.

If this works in adult human cells, it will be a huge advantage for the clinical applications of iPS cells.

Shinya Yamanaka, Kyoto University

Four years ago, Sergiy Velychko, a graduate student at the Max Planck Institute for Molecular Biomedicine in Hans Schlers lab, and his team were studying the role of Oct4 in creating iPS cells from mouse embryonic fibroblasts. He used vectors to introduce various mutations of the gene coding for Oct4 to the cells he was studying, along with a negative controlone that didnt deliver any Oct4. He was shocked to discover that even using his negative control, he was able to generate iPS cells.

Velychkos experiment was suggesting that it is possible to develop iPS cells with only SKM.

We just wanted to publish this observation, Velychko tells The Scientist, but he knew hed need to replicate it first because reviewers wouldnt believe it.

He and his colleagues, including Guangming Wu, a senior scientist in the lab, repeated the experiment several times, engineering vectors with different combinations of the four factors. SKMthe combination that didnt include Oct4was able to induce pluripotency in the cells with about 30 percent of the efficiency of OSKM, but the cells were of higher quality, meaning that the researchers didnt see evidence of common off-target epigenetic effects. They reported their results yesterday (November 7) in Cell Stem Cell.

Efficiency is not important. Efficiency means how many colonies do you get, explains Yossi Buganim, a stem cell researcher at the Hebrew University of Jerusalem, who was not involved in the study. If the colony is of low quality, the chances that eventually the differentiated cells will become cancerous is very high.

Finally, the team employed the ultimate test, the tetraploid complementation assay, in which iPS cells are aggregated with early embryos that otherwise would not have been able to form a fully functional embryo on their own. These embryos grew into mouse pups, meaning that the iPS cells the team created were capable of maturing into every type of cell in the animal.

Whats more is they found that the SKM iPS cells could develop into normal mouse pups 20 times more often than the OSKM iPS cells, suggesting that the pluripotency of iPS cells can be greatly improved by omitting Oct4 from the reprogramming factor cocktail.

The results will need to be verified in human cells, Buganim cautions. His team has developed methods for creating iPSCs that worked well in mouse cells only to be completely ineffective in humans.

Yamanaka himself was enthusiastic about the results, telling The Scientist in an email that his team would definitely try the method in other cell types, especially adult human blood cells and skin fibroblasts. If this works in adult human cells, it will be a huge advantage for the clinical applications of iPS cells.

S.Velychkoet al.,Excluding Oct4 from Yamanaka cocktail unleashes the developmental potential of iPSCs,Cell Stem Cell,doi:10.1016/j.stem.2019.10.002,2019.

Emma Yasinski is a Florida-based freelance reporter. Follow her on Twitter@EmmaYas24.

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Oct4, Considered Vital for Creating iPSCs, Actually Isnt Needed - The Scientist

A winding romp through advances in cell biology pushes readers to ponder the boundaries of life – Science Magazine

Philip BallUniversity of Chicago Press2019384 pp.Purchase this item now

A small bundle of human nerve cells are being cultured in a petri dish. The cells divide. They differentiate into cell types found in the brain. The cell network grows dense and develops brain-like structureslayers and folds. The cells begin to signal. The brain cell cluster has been derived from skin cells harvested from science writer Philip Balls shoulder.

The scientists who created Balls skin-turned-brain organoid study brain development and want to understand the basis of neurodegeneration. But what exactly goes on inside these cell aggregates, and could we reach a point at which they are more brain than brain-like?

Biologists can also build embryo-like structures (embryoids) from human stem cells, which can be used to study early prenatal development. However, synthetic embryos can develop certain featuressuch as the primitive streak, a structure that establishes bilateral symmetry in an organismthat mark, for some, the transition from embryo to individual human being.

Balls experience grappling with how to think about these living structures, as documented in his new book, How to Grow a Human, is part of a larger question with which humanity has wrestled for centuries: What is life, and how might our understanding of it change with our ever-increasing capability to manipulate it?

The book offers a provocative, meandering take on the progression of groundbreaking biotechnological capabilities. For example, in chapter 3, Ball explores the dawn of tissue culture at the turn of the 20th century and the motivations of the scientists who conducted the research. Ross Harrison sought to settle a debate between Camillo Golgi and Santiago Ramny Cajal over the makeup of nervous systems; the former argued that nervous systems were one uninterrupted structure, whereas the latter believed there to be distinct nerve cells. Along the way to showing that nerve fibers lengthen through nerve cell proliferation, confirming Ramny Cajals hypothesis, Harrison was the first to develop a technique to keep tissues alive with active cell growth in vitro, sustaining amphibian embryonic tissue in jars.

Alexis Carrel, on the other hand, was a white supremacist striving to preserve a superior stock of humankind. Carrel and his team iterated on and applied Harrisons method to many different tissues, including those of birds, embryonic chickens, and, of course, humans. Here, Ball also works in how science fiction writing was influenced by early advances in cell biology, describing Julian Huxleys The Tissue-Culture King, which centers on a biologist who redesigns members of a remote tribe and builds living objects of worship from the flesh of the tribes king. Although interesting, asides such as this disrupt the narratives continuity.

Balls writing is most absorbing when he reflects on boundary-pushing research, such as advances toward converting human skin cells to eggs or sperm or the promise of approaches for fabricating human organs to help people who need transplants. In chapter 5, for example, he describes experiments in which rat cells formed pancreases in mice, and others in which human cells survived in pig and cattle embryos, and then considers how governments and the public might approach the prospect of harvesting human organs grown in other animals.

Discussing how and where we have drawn ethical and legal lines for procedures such as in vitro fertilization and preimplantation genetic diagnosis (PGD) of embryos, Ball contemplates what historical precedent may mean for the governance of emerging biotechnological capabilities. Unlike in the United Kingdom, where PGD is permitted only to avoid implanting an embryo with a serious heritable disease, the United States does not regulate PGD-enabled embryo selection at the federal level, meaning PGD can be used to select for offspring of a particular gender or to rule out embryos that have an elevated risk of intellectual disability. (As Ball points out, it may be possible to adapt this testing to screen for embryos that are predicted to have exceptional cognitive ability.)

At the center of an adjacent debate are germline genome-editing technologies. As exemplified by the so-called CRISPR-baby controversy and expounded upon by Ball, access to, and affordability of, new biotechnologies may serve some segments of society while underserving others. Ball appeals to the democratic process to determine the balance between personal liberty and state-dictated equity, acknowledging that everyone has a stake in and therefore the right to be heard on this important issue.

Because of the immense power of emerging biotechnologies, those of us who are intimately involved with these advances must make a concerted effort to equip both policy-makers and the public with the knowledge and tools needed to navigate this evolving landscape. Ambitious and expansive, How to Grow a Human could be one piece of this effortBalls look at the state of human-facing cutting-edge bioscience is a thought-provoking read

The reviewer co-leads the Congressional Science Policy Initiative at the Federation of American Scientists, Washington, DC 20036, USA

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A winding romp through advances in cell biology pushes readers to ponder the boundaries of life - Science Magazine