Category Archives: Somatic Stem Cells

Stem cell therapy is for animals too – SciTech Europa

Stem cell therapy for animals has seen breakthroughs

Stem cell therapy is increasingly becoming a more mainstream form of medicine. Usually applied to humans, the use of this regenerative treatment is now also being extended to animals including cats and dogs. Regenerative medicine, particularly stem cell treatment has seen many advancements in recent years with some groundbreaking studies coming to light.

Taking the cells from bone marrow, umbilical cords, blood or fat, stem cells can grow to become any kind of cell and the treatment has seen many successes in animals. The regenerative therapy has been useful particularly for treatment of spinal cord and bone injuries as well as problems with tendons, ligaments and joints.

Expanded Potential Stem Cells (EPSCs) have been obtained from pig embryos for the first time. The cells offer groundbreaking potential for studying embryonic development and producing transnational research in genomics and regenerative medicine, biotechnology and agriculture.

The cells have been efficiently derived from pig preimplantation embryos and a new culture medium developed in Hong Kong and Cambridge enabled researchers from the FLI to establish permanent embryonic stem cell lines. The cells have been discovered in a collaboration between research groups from the Institute of Farm Animal Genetics at the Friedrich-Loeffler-Institut (FLI) in Mariensee, Germany, the Wellcome Trust Sanger Institute in Cambridge, UK and the University of Hong Kong, Li Ka Shing Faculty of Medicine, School of Biomedical Sciences.

Embryonic stem cells (ESC) are derived from the inner cells of very early embryos, the so-called blastocysts. Embryonic stem cells are all-rounders and can develop into various cell types of the body in the culture dish. This characteristic is called pluripotency. Previous attempts to establish pluripotent embryonic stem cell lines from farm animals such as pigs or cattle have resulted in cell lines that have not really fulfilled all properties of pluripotency and were therefore called ES-like.

Dr Monika Nowak-Imialek of the FLI said: Our porcine EPSCs isolated from pig embryos are the first well-characterized cell lines worldwide. EPSCs great potential to develop into any type of cell provides important implications for developmental biology, regenerative medicine, organ transplantation, disease modelling and screening for drugs.

The stem cells can renew themselves meaning they can be kept in culture indefinitely, and also show the typical morphology and gene expression patterns of embryonic stem cells. Somatic cells have a limited lifespan, so these new stem cells are much better suited for long selection processes. It has been shown that these porcine stem cell lines can easily be modified with new genome editing techniques such as CRISPR/Cas, which is particularly interesting for the generation of porcine disease models.

The EPSCs have a high capacity to develop not only into numerous cell types of the organism, but also into extraembryonic tissue, the trophoblasts, making them very unique and lending them their name. This capacity could prove valuable for the future promising organoid technology, where organ-like small cell aggregations are grown in 3D aggregates that can be used for research into early embryo development, various disease models and testing of new drugs in petri dishes. In addition, the authors were able to show that trophoblast stem cells can be generated from their porcine stem cells, offering a unique possibility to investigate functions or diseases of the placenta in vitro.

A major hurdle to using neural stem cells derived from genetically different donors to replace damaged or destroyed tissues, such as in a spinal cord injury, has been the persistent rejection of the introduced material (cells), necessitating the use of complex drugs and techniques to suppress the hosts immune response.

Earlier this year, an international team led by scientists at University of California San Diego School of Medicine successfully grafted induced pluripotent stem cell (iPSC)-derived neural precursor cells back into the spinal cords of genetically identical adult pigs with no immunosuppression efforts. The grafted cells survived long-term, displayed differentiated functionality and caused no tumours.

The researchers also demonstrated that the same cells showed similar long-term survival in adult pigs with different genetic backgrounds after only short course use of immunosuppressive treatment once injected into injured spinal cord.

Senior author of the paper Martin Marsala, MD, professor in the Department of Anesthesiology at UC San Diego School of Medicine said: The promise of iPSCs is huge, but so too have been the challenges. In this study, weve demonstrated an alternate approach.

We took skin cells from an adult pig, an animal species with strong similarities to humans in spinal cord and central nervous system anatomy and function, reprogrammed them back to stem cells, then induced them to become neural precursor cells (NPCs), destined to become nerve cells. Because they are syngeneic genetically identical with the cell-graft recipient pig they are immunologically compatible. They grow and differentiate with no immunosuppression required.

Co-author Samuel Pfaff, PhD, professor and Howard Hughes Medical Institute Investigator at Salk Institute for Biological Studies, said: Using RNA sequencing and innovative bioinformatic methods to deconvolute the RNAs species-of-origin, the research team demonstrated that pig iPSC-derived neural precursors safely acquire the genetic characteristics of mature CNS tissue even after transplantation into rat brains.

NPCs were grafted into the spinal cords of syngeneic non-injured pigs with no immunosuppression finding that the cells survived and differentiated into neurons and supporting glial cells at all observed time points. The grafted neurons were detected functioning seven months after transplantation.

Then researchers grafted NPCs into genetically dissimilar pigs with chronic spinal cord injuries, followed by a transient four-week regimen of immunosuppression drugs again finding long-term cell survival and maturation.

Marsala continued: Our current experiments are focusing on generation and testing of clinical grade human iPSCs, which is the ultimate source of cells to be used in future clinical trials for treatment of spinal cord and central nervous system injuries in a syngeneic or allogeneic setting.

Because long-term post-grafting periods between one and two years are required to achieve a full grafted cells-induced treatment effect, the elimination of immunosuppressive treatment will substantially increase our chances in achieving more robust functional improvement in spinal trauma patients receiving iPSC-derived NPCs.

In our current clinical cell-replacement trials, immunosuppression is required to achieve the survival of allogeneic cell grafts. The elimination of immunosuppression requirement by using syngeneic cell grafts would represent a major step forward said co-author Joseph Ciacci, MD, a neurosurgeon at UC San Diego Health and professor of surgery at UC San Diego School of Medicine.

Other recent advancements include the advancement toward having a long-lasting repair caulk for blood vessels. A new method has been for generating endothelial cells, which make up the lining of blood vessels, from human induced pluripotent stem cells. When endothelial cells are surrounded by a supportive gel and implanted into mice with damaged blood vessels, they become part of the animals blood vessels, surviving for more than 10 months.

The research was carried out by stem cell researchers at Emory University School of Medicine and could form the basis of a treatment for peripheral artery disease, derived from a patients own cells.

Young-sup Yoon, MD, PhD, who led the team, said: We tried several different gels before finding the best one. This is the part that is my dream come true: the endothelial cells are really contributing to endogenous vessels.

When cells are implanted on their own, many of them die quickly, and the main therapeutic benefits are from growth factors they secrete. When these endothelial cells are delivered in a gel, they are protected. It takes several weeks for most of them to migrate to vessels and incorporate into them.

Other groups had done this type of thing before, but the main point is that all of the culture components we used would be compatible with clinical applications.

This research is particularly successful as previous attempts to achieve the same effect elsewhere had implanted cells lasting only a few days to weeks, using mostly adult stem cells, such as mesenchymal stem cells or endothelial progenitor cells. The scientists also designed a gel to mimic the supportive effects of the extracellular matrix. When encapsulated by the gel, cells could survive oxidative stress inflicted by hydrogen peroxide that killed unprotected cells. The gel is biodegradable, disappearing over the course of several weeks.

The scientists tested the effects of the encapsulated cells by injecting them into mice with hindlimb ischemia (restricted blood flow in the leg), a model of peripheral artery disease.

After 4 weeks, the density of blood vessels was highest in mice implanted with gel-encapsulated endothelial cells. The mice were nude, meaning genetically immunodeficient, facilitating acceptance of human cells.

The scientists found that implanted cells produce pro-angiogenic and vasculogenic growth factors. In addition, protection by the gel augmented and prolonged the cells ability to contribute directly to blood vessels. To visualise the implanted cells, they were labelled beforehand with a red dye, while functioning blood vessels were labelled by infusing a green dye into living animals. Implanted cells incorporated into vessels, with the highest degree of incorporation occurring at 10 months.

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Stem cell therapy is for animals too - SciTech Europa

Stem Cell Therapy Industry 2019 Global Market Size, Trends, Revenue, Growth Prospects, Key Companies and Forecast by 2023 – Markets Gazette

Bone marrow transplant is the most widely used stem-cell therapy, but some therapies derived from umbilical cord blood are also in use. Research is underway to develop various sources for stem cells, and to apply stem-cell treatments for neurodegenerative diseases and conditions, diabetes, heart disease, and other conditions.

With the ability of scientists to isolate and culture embryonic stem cells, and with scientists growing ability to create stem cells using somatic cell nuclear transfer and techniques to create induced pluripotent stem cells, controversy has crept in, both related to abortion politics and to human cloning. Additionally, efforts to market treatments based on transplant of stored umbilical cord blood have been controversial.

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Scope of the Report:

This report studies the Stem Cell Therapy market status and outlook of Global and major regions, from angles of players, countries, product types and end industries; this report analyzes the top players in global market, and splits the Stem Cell Therapy market by product type and applications/end industries.

USA is a huge market, and the total sum of the industry is more than 24 Million US dollars in 2014. At the same time, this industry continuously increases, with the development of global economy.

According to the research, the most potential market in the main countries of stem cell therapy industry is China, determined by the rising level of medical care. Besides, South America, Middle East should also be focused by the investors. They are the potential consumers of stem cell therapy.

Complete report on Stem Cell Therapy Market report spread across 139 pages, profiling 18 companies and supported with tables and figures.

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Development policies and plans are discussed as well as manufacturing processes and cost structures are also analyzed. This report also states import/export consumption, supply and demand Figures, cost, price, revenue and gross margins. The report focuses on global major leading Stem Cell Therapy Industry players providing information such as company profiles, product picture and specification, capacity, production, price, cost, revenue and contact information. Upstream raw materials and equipment and downstream demand analysis is also carried out. The Stem Cell Therapy industry development trends and marketing channels are

Analysis of Stem Cell Therapy Industry Key Manufacturers:

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This report studies the top producers and consumers, focuses on product capacity, production, value, consumption, market share and growth opportunity in these key regions, covering:

Market Segment by Type, covers

Market Segment by Applications, can be divided into

Table of Contents

There are 15 Chapters to deeply display the global Banknote-Printing Machine market.

Chapter 1, to describe Banknote-Printing Machine Introduction, product scope, market overview, market opportunities, market risk, market driving force

Chapter 2, to analyze the top manufacturers of Banknote-Printing Machine, with sales, revenue, and price of Banknote-Printing Machine, in 2016 and 2017;

Chapter 3, to display the competitive situation among the top manufacturers, with sales, revenue and market share in 2016 and 2017;

Chapter 4, to show the global market by regions, with sales, revenue and market share of Banknote-Printing Machine, for each region, from 2013 to 2018;

Chapter 5, 6, 7, 8 and 9, to analyze the market by countries, by type, by application and by manufacturers, with sales, revenue and market share by key countries in these regions;

Chapter 10 and 11, to show the market by type and application, with sales market share and growth rate by type, application, from 2013 to 2018;

Chapter 12, Banknote-Printing Machine market forecast, by regions, type and application, with sales and revenue, from 2018 to 2023;

Chapter 13, 14 and 15, to describe Banknote-Printing Machine sales channel, distributors, traders, dealers, Research Findings and Conclusion, appendix and data source.

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Stem Cell Therapy Industry 2019 Global Market Size, Trends, Revenue, Growth Prospects, Key Companies and Forecast by 2023 - Markets Gazette

Significant Growth Foreseen by Stem Cell Therapies Market During 2015 2025 – Rapid News Network

Stem cells are undifferentiated biological cells, and having remarkable potential to divide into any kind of other cells. When a stem cell divides, each new cell will be a new stem cell or it will be like another cell which is having specific function such as a muscle cell, a red blood cell, brain cell and some other cells.

There are two types of stem cells

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Stem cells harvested from umbilical cord blood just after birth. And this cells can be stored in specific conditions. Stem cells also can be harvest from bone marrow, adipose tissue.

Embryonic cells can differentiate into ectoderm, endoderm and mesoderm in developing stage. Stem cells used in the therapies and surgeries for regeneration of organisms or cells, tissues.

Stem cells are used for the treatment of Gastro intestine diseases, Metabolic diseases, Immune system diseases, Central Nervous System diseases, Cardiovascular diseases, Wounds and injuries, Eye diseases, Musculoskeletal disorders.

Harvesting of Adult cell is somewhat difficult compare to embryonic cells. Because Adult cells available in the own body and it is somewhat difficult to harvest.

Stem Cell TherapiesMarket: Drivers and Restraints

Technology advancements in healthcare now curing life threatening diseases and giving promising results. Stem Cell Therapies having so many advantages like regenerating the other cells and body organisms. This is the main driver for this market. These therapies are useful in many life threatening treatments. Increasing the prevalence rate of diseases are driven the Stem Cell Therapies market, it is also driven by increasing technology advancements in healthcare. Technological advancements in healthcare now saving the population from life threatening complications.

Increasing funding from government, private organizations and increasing the Companies focus on Stem cell therapies are also driven this market

However, Collecting the Embryonic Stem cells are easy but Collecting Adult Stem cell or Somatic Stem cells are difficult and also we have to take more precautions for storing the collected stem cells.

Stem Cell TherapiesMarket: Segmentation

Stem Cell Therapies are segmented into following types

Based on treatment:

Based on application:

Based on End User:

Stem Cell TherapiesMarket: Overview

With rapid technological advantage in healthcare and its promising results, the use of Stem Cell Therapies will increase and the market is expected to have a double digit growth in the forecast period (2015-2025).

Stem Cell TherapiesMarket: Region- wise Outlook

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Depending on geographic regions, the global Stem Cell Therapies market is segmented into seven key regions: North America, South America, Eastern Europe, Western Europe, Asia Pacific excluding Japan, Japan and Middle East & Africa.

The use of Stem Cell Therapies is high in North America because it is highly developed region, having good technological advancements in healthcare setup and people are having good awareness about health care. In Asia pacific region china and India also having rapid growth in health care set up. Europe also having good growth in this market.

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Significant Growth Foreseen by Stem Cell Therapies Market During 2015 2025 - Rapid News Network

Blast Off With Rocket Pharmaceuticals – Seeking Alpha

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Rocket Pharmaceuticals (RCKT) is a best in class gene therapy company with five shots on goal and strong data to support its current valuation. The two largest assets, RP-L102, a lentiviral gene therapy for Fanconi Anemia and RP-A501, an AAV gene therapy for Danon Disease are each worth multiples of the current share price, if successfully commercialized. The management team is highly experienced and have successfully commercialized many products at predecessor companies. The board of directors are both experienced and proven money makers on wall street in the world of biotech. The shareholder base is strong with top quality investors and the company has sufficient cash on the balance sheet for at least two years, during which multiple value drivers will report out. Commercialization of the most advanced products could occur in the 2021 timeframe. While never an investment attribute alone, I would note that there have been multiple acquisitions in gene therapy during the last 18 months (AVXS, ONCE) at eye-watering valuations and large cap pharma is struggling to find pipeline assets and return on productivity for internal pipeline assets remains at a multi decade low.

This report provides an overview of the company and details of the most advanced product in development, RP-L102 for Fanconi Anemia, as this is the primary focus for investors currently. The company's largest pipeline asset, RP-A501 for Danon Disease will become a focus for investors during 2020.

RCKT has Five Programs. Four will be in the Clinic in 2019

Source: Company data

Pipeline has > $1bn in Revenue Potential

Source: Company data, my estimates

Plenty of Catalysts Anticipated During Next 12 months

With five assets either in, or almost in the clinic, there are multiple catalysts expected during the next twelve months.

Source: Company data, my estimates

The company finished 2Q 2019 with $257 million of cash on its balance sheet and during the last 12 months the company burnt $66.5 million of cash. This is expected to increase during 2020 and 2021 as multiple pivotal trials start and consensus forecasts suggest that the company will spend $99 million in 2020 and $98.5 million in 2021. Therefore the company has sufficient cash on its balance sheet for approximately 2.5 years during which time, there will be multiple clinical catalysts that will hopefully drive the share price higher, allowing the company to raise additional equity in late 2020 to fund the company to break even in the 2023 timeframe. In the current environment, investors need to avoid any company that requires substantial financing.

Rocket Pharmaceuticals trades with a market capitalization of just $546 million. As of June 30, 2019, the company had cash of $ 258 million and debt of $ 46 million. Compared to other companies in the gene therapy space, RCKT trades at a significant discount. The company is well capitalized with approximately two years of cash on the balance sheet and there are a number of value creating catalysts during the next 12 months. Additionally, whilst never a reason to solely own a biotech company, I would note that there have been a number of acquisitions in the gene therapy space during the past few years. Large-cap pharma and biotech is short on products and long on cash and they need to make acquisitions.

Selected M&A in the Gene Therapy Sector: 2016-2019

Source: Bloomberg, Company data

RCKT is currently covered by 8 Wall Street Sell Side analysts, as shown below. Notably, Large banks including Goldman Sachs, Jefferies, JP Morgan, Morgan Stanley, Citi and Barclays Capital are all missing. As the company evolves into a commercial company during the next several years, it is likely that some of these brokers will initiate coverage of the stock, thereby improving liquidity.

Source: Bloomberg

As with all biotechnology stocks, there are significant risks associated with this investment and under a worst case outcome, there is 100% downside. The most obvious risk is that the pipeline products fail in clinical development. While Rocket has five assets in its pipeline, and success in any one of these is likely enough to justify the current valuation, negative clinical trial data would clearly have a negative impact on the company's share price. Under the outcome that all five pipeline assets fail in development, the stock is likely worth zero.

We are also in an uncertain political environment with an election looming in 2020. It is unlikely that either party will be arguing for higher drug prices and biotech stocks often underperform during these periods. Investors can mitigate this risk by being short a number of lower quality biotech companies and long a number of higher quality biotech companies. In my opinion, investors need to be long biotech stocks that are financed through 2021 and have multiple catalysts during the next 12 months. Being short companies in the opposite camp likely generates a good return as well.

Currently this company is not really exposed to foreign exchange rate or interest rate risks but these factors may become relevant in years to come.

This report will start with a primer on exactly what gene therapy is and then a detailed analysis of Rocket's lead asset where clinical data has been evolving during the last 24 months.

Gene therapy refers to technologies that can insert genes into cells, thereby expressing the proteins encoded by the genes. Gene therapies consist of two key elements - the gene of interest, and a vector that carries the gene into the host's target cells. Over the years a number of vectors have been used, although most efforts now employ viruses to carry the target genes. In creating a gene therapy, most of the viral genome is replaced by the therapeutic gene of interest. This eliminates the ability of the virus to replicate and cause disease, and permits relatively large target genes to be carried. The manipulated genome is inserted into a viral vector and when the virus is given to a patient, it is taken up by the patient's cells where it delivers its DNA to the nucleus. The cell then makes the target protein using the new gene as if it were encoded by the cell's own genetic material. Importantly, this process of gene transfer can be conducted ex vivo or in vivo depending upon the application.

Although gene therapy has the potential to treat a wide range of conditions, orphan monogenic diseases are particularly well suited for this approach. There are a number of scientific, economic, and logistical attributes of severe, monogenic orphan diseases that make them ideal candidates for the development of gene therapies by small biotechnology companies. First, by their nature as monogenic diseases, their causes are defects in a single gene. The pathogenesis of the disease is often well understood, and its treatment can be straightforward: by placing a functional copy of the gene in affected tissues, the disease process can be functionally cured/halted. Second, as orphan disorders affect a relatively small number of patients, on the order of several thousand individuals, the clinical trial programs can be conducted in tens of patients, rather than thousands. Such trials are less expensive to run and the logistics are within the capabilities of even small biotech companies. Third, most monogenic orphan diseases have no currently available disease altering therapies. Therefore the unmet need is high and any safe and effective therapy will likely be embraced. Fourth, the FDA has been flexible in its requirements for licensure in severe orphan diseases, routinely granting accelerated approvals based on surrogate markers that are reasonably likely to predict clinical benefit. Finally, innovative, and effective orphan therapies still have pricing flexibility in most worldwide markets such that companies can achieve attractive risk-adjusted returns on their research and development investment. Therefore, the orphan business model is well established and has repeatedly generated high returns for small cap biotechnology companies.

Rocket is building a comprehensive gene therapy technology platform to address serious, rare diseases. Rocket is developing both ex vivo lentiviral-based gene therapy technologies as well as adeno-associated virus (AAV) technologies to be used in vivo. Rocket also has early preclinical efforts in gene editing such as CRISPR/Cas9 (Clustered Regularly Interspaced Short palindromic Repeat/CRISPR-associated protein-9 nuclease) in its pipeline.

RCKT is Focusing on both In Vivo and Ex Vivo Gene Therapies

Source: Company data

What is a Lentiviral Vector?

Lentiviruses are a genus of retroviruses that includes the human pathogen human immunodeficiency virus (HIV). Like all retroviruses, lentiviruses are RNA viruses that encode reverse transcriptase (RT). Once a virion infects a cell, RT converts the virus' RNA genome into a DNA copy. This DNA copy is then integrated into the host genome using the virally encoded integrase. Once integrated into the host genome, the virally encoded genes are expressed and copied alongside host genes using the normal host gene expression and replication machinery. Lentivirus-based gene therapy approaches seek to co-opt the viral integration process to stably introduce genes of therapeutic interest into the human genome. Unfortunately, every insertion event is associated with a theoretical risk of causing disease (insertional mutagenesis) due to disruption of the host genome at the site of integration. As a result, lentiviral gene therapy programs take several steps to limit the ability of the virus to generate unnecessary insertion events.

Lentiviral (and retroviral more generally) gene therapy is most often deployed in an ex vivo process whereby cells are removed from the body, transfected with a lentivirus encoding the gene of interest, and then reintroduced into the patient. In Rocket's programs, it is transducing hematopoietic stem cells (HSCs) isolated from patients with defined monogenic diseases in order to insert a normal copy of the gene that is defective in these patients. The transduced HSCs are then infused back into the patient so that they will engraft. Although historically the patient's native hematopoietic system is ablated to improve engraftment, Rocket and its academic collaborators have pioneered a lentiviral approach that requires no or minimal chemotherapy.

HSCs are a self-renewing cell type that reconstitutes the patient's hematopoietic system, thus providing permanent, life-long expression of the normal gene from this one-time treatment. Because HSCs differentiate to form a variety of terminal cell types, this general approach is potentially applicable to a variety of genetic diseases in a modular, repeatable fashion. The ex vivo use of HSCs rather than in vivo treatment of all cells dramatically reduces the number of insertion events required to generate a therapeutic effect thereby reducing the risk of insertional mutagenesis. In addition, Rocket's use of the patient's own cells (an autologous transplant) is an important attribute of lentiviral gene therapy, as this should avoid some of the serious immune complications associated with allogeneic transplants such as graft-versus host disease (GVHD), which require management with harsh immunosuppressive therapies and can be fatal.

The lentiviral vector Rocket uses is based on the HIV virus. The vector takes advantage of the virus' natural ability to integrate into the host genome in both dividing and nondividing cells in order to efficiently deliver the chosen genetic payload. However the vector has been modified in a number of ways to render it nonpathogenic. Virtually all the viral genes have been removed to make room for the transgene and eliminate the virus' ability to replicate. The infectious viral particles are generated by co-transfecting producer cells with separate plasmids containing the "gutted" viral backbone and transgene, the viral capsid proteins and viral polymerase to make viral RNA from the DNA plasmid, reverse transcriptase to make DNA from the virus' RNA, and VSV - a pantropic envelope protein that allows infection of a variety of human cell types (not just CD4+ T cells). This results in the production of infectious viral particles carrying the viral RNA, reverse transcriptase protein, and viral integrase protein. When the virus infects target cells, it is thus able to undergo the process of reverse transcription and integration into the genome, but because the natural viral genes are not present, it can only undergo this single cycle of transduction and cannot replicate or infect other cells. To make doubly sure of this, the terminal ends of the viral genome are also modified to be "self-inactivating," so that they would no longer be recognized for excision even if the necessary viral proteins were to become present in the cell. Thus, the transgene is stably inserted into the host genome. For those readers who would like additional information on lentival gene therapy I recommend you reed this report available on PubMed. Kenneth Lundstrom does a great job discussing the pros and cons of each approach.

AAV is a naturally occurring non-pathogenic virus that is not known to cause any disease in humans. AAV has a number of advantages as a delivery vehicle for in vivo applications of gene therapy. AAV vectors do not replicate inside the host cell, preventing their spread to unintended tissues, and they typically integrate at a very low level into the host cell's genome, reducing the risk of insertional mutagenesis. Moreover, cellular tropism can be effectively modulated by using the natural tropism of different AAV serotypes, synthetically engineering the AAV capsid, and/or altering the transgene's promoter sequence. AAV vectors are also able to transduce non-dividing cells (such as RPE cells in the retina), and once incorporated into a host cell, they can drive the expression of a therapeutic protein for years. Last, AAV vectors can carry a good amount of genetic material, up to 4.5kb permitting them to target a range of indications. Since AAVs are non-replicating and generally non-integrating, the viral genome is typically not copied when an infected cell divides. Therefore, there is a theoretical risk that the efficacy of AAV based therapy in dividing cells could wane as an increasing number of divisions occurs.

A large number of clinical trials of AAV gene therapy are either under way, or have been completed. Applications have been diverse, ranging from hemophilia to REP65-mediated blindness and Parkinson's disease. AAV is versatile, and can be delivered through a number of routes of administration including intravenous, intramuscular, intrapleural, intravitreal, subretinal, and intracranial. For example, in lysosmal storage disorder (LSD) and hemophilia, AAV gene therapies are delivered systemically via intravenous (i.v.) route of administration and liver cells are transduced. In more localized diseases such as retinal dystrophy, choroideremia, X-linked retinoschisis (XLRS), the gene therapies are directly injected into the eye. In advanced Parkinson's disease, the gene therapy candidate is injected intracranially.

Fanconi Anemia - A rare disease with limited treatment options and a median survival of 29 years

Fanconi Anemia (FA) is a rare autosomal recessive DNA repair-deficiency syndrome characterized by aplastic anemia and progressive bone marrow failure. Though FA is a blood disorder, broad complications across a number of organ systems are associated with the syndrome such as defects of the eyes, ears, bones, kidneys and the heart. Perhaps most important, up to 30% of patients with FA develop leukemia, myelodysplastic syndrome (MDS), and or solid tumors at ages between 5 and 15. The median life span for FA patients is approximately 29 years.

Disease Progression: Unmet need for a treatment for FA

Source: Kutler et al, Blood 101:1249, 2003

FA is a complex disease with abnormalities in at least 18 genes associated with the disorder. These genes typically belong in the FANC gene family (FANC A-G, FANC CJ, FANC CL, and FANC M). The FANC gene family is associated with the DNA repair pathway. A mutation in any of these genes renders cells unable to properly repair damaged DNA. FANC A, B, C, E, F, G, L and M) form a nuclear complex termed the FA core complex. The FA core complex is required for monoubiquitination of the FANCD2 protein. Monoubiquintination of the FANCD2 protein allows for FANCD2 to translocate to sites of DNA damage to facilitate BRCA2/FAN CD1 and FANC E function in homologous recombination for DNA repair. Due to mutations in this DNA repair machinery, FA patients are simply unable to repair DNA damage that occurs naturally as cells divide, are exposed to mutagens, etc. Depending upon the exact DNA insult that occurs, unrepaired DNA can lead to abnormal cell death (most commonly) or uncontrolled cell growth. The abnormal cell death in turn creates FA's characteristic anemia and other organ defects. In other cases unrepaired DNA damage leads to uncontrolled cell growth and the development of a leukemia, tumor, or MDS. While it is extremely uncommon for any one DNA insult to generate cancer rather than cell death, DNA damage is occurring constantly within millions of cells in any human. Therefore, with millions of potentially oncogenic unrepaired mutations occurring it is unsurprising that FA patients have a significantly increased risk of developing cancer.

Approximately 60% of FA cases are due to mutations in the FANC A gene (the specific genetic abnormality that Rocket's lead program addresses). Approximately half of FA patients are diagnosed prior to age 10 while about 10% are diagnosed during adulthood. The remaining ~40% of FA patients are diagnosed during their teenage years. Birth defects such as undeveloped skull, eyes, or abnormalities in radial bones, kidney, skeleton, or skin pigmentation often facilitate early diagnosis. The definitive test for FA is a chromosome breakage test using crosslinking agents (dieposxybutane or mitomycin C) in isolated patient blood cells. While blood cells from healthy volunteers are able to correct most of the crosslinking agent induced DNA damage, FA patients' cells are incapable of correcting the damage from DEB or MMC treatment. Other methods of diagnosis include the use of molecular genetic testing on the 18 genes associated with FA such as sequencing analysis. The only curative therapy for FA is hematopoietic stem cell transplantation (HSCT) (there is good information on this here).

However, HSCT has a number of notable difficulties and complications. For one, it can be difficult to find a matched donor so that the transplant can be performed with a reasonable likelihood of success. Even when a suitable match is found, HSCT confers a high degree of morbidity and mortality, particularly in FA patients. Recent advances in conditioning regimens and supportive care have reduced treatment-related mortality from 38% or higher to 5-10% at most centers; nonetheless, such rates of death due to the procedure are notable. Moreover, HSCT can have major short and long-term complications including veno-occlusive disease, infections, infertility, secondary malignancies and graft-versus-host disease. GvHD can be particularly problematic and can evolve into a life-long condition causing serious damage to the lung, skin and mucosa. In severe cases GvHD can also be deadly. Conditioning chemotherapy is also inherently mutagenic and is therefore associated with additional risk of tumors developing post-transplant (secondary malignancy). FA patients are unable to repair these mutations that occur throughout the body during conditioning. Therefore HSCT confers a particularly high risk of secondary malignancy to FA patients. For example, the chance of an FA patient developing a new malignancy such as squamous cell carcinoma is estimated to be ~4x higher post HSCT. Thus, while HSCT is curative of FA's characteristic hematological manifestations, "cured" patients remain at an elevated risk of experiencing morbidity/mortality.

There can be spontaneous improvement in a small fraction of FA patients due to somatic mosaicism. Somatic mosaicism results from the spontaneous, random mutations that occur during normal cell division and proliferation. The cells clonally derived from the initial mutant cell have a different genotype than their neighbors. Somatic mosaicism has been reported in patients with FA. In cells of FA patients, the reversion of a pathogenic FA allele to a functional wild type allele confers a survival advantage on the cell vs. its non-reverted sibling cells. The cell(s) with the wild type reversion exploit this survival advantage to gradually populate the bone marrow. Up to 10-15% of FA patients develop somatic mosaicism resulting in disease stabilization or even improvement in bone marrow function for a prolonged period of time. This observation supports the theory that a very small percentage of corrected cells is sufficient to change the clinical course of FA. Somatic mosaicism therefore provides a rational as to why gene therapy may be successful in the treatment of FA patients and RCKT refer to somatic mosaicism as natural gene therapy.

Somatic mosaicism in FA leads to stabilization/correction of blood counts, in some cases for decades. This uncommon variant results from a reverse mutation and demonstrates that a modest number of gene-corrected hematopoietic stem cells can repopulate a patient's blood and bone marrow with corrected (non-FA) cells.

Source: Soulier, J., et al. (2005) Detection of somatic mosaicism and classification of Fanconi anemia patients by analysis of the FA/BRCA pathway. Blood 105: 1329-1336

Commercial launch likely in 2021/22 with >$1bn potential.

RP-L102 is a lentiviral vector that employs the phosphoglycerate kinase (PGK) promoter to express the FANCA gene. Expression is further facilitated by inclusion of the Woodchuck Hepatitis virus posttranscriptional regulatory element (WPRE). RP-L102 was licensed from the Centro de Investigaciones Energeticas, Medioambientales Y Technologicas (CIEMAT) in Madrid, Spain. CIEMAT is the Investigational Medicinal Product Dossier (IMPD) sponsor of the ongoing Phase I/II FANCOLEN-1 study of RP-L102 in patients with FA. Rocket is entitled to the data and commercial rights to the drug product generated under the CIEMAT sponsored IMPD.

RP-L102 gene therapy could have significant advantages over HSCT for FA patients. Perhaps the most notable advantage is that RP-L102 is being developed by Rocket and its academic collaborators without the use of bone marrow conditioning with chemotherapy agents. In contrast, all HSCT protocols require chemotherapy conditioning. The lack of conditioning confers a number of advantages. For example, without the use of chemotherapy agents, patients do not need to be hospitalized, and treatment can occur outside of a transplant-unit. Most important, FA patients have a diminished ability to correct damage to genetic material like that typically caused by chemotherapeutic agents. Therefore, by avoiding chemotherapy conditioning, the FA patients should not have an increased risk of head and neck cancer or leukemia. Moreover, because of their toxicities in FA bone marrow transplants are indicated specifically for patients with signs of bone marrow failure. RPL102 should enable treatment earlier in the disease course, well before bone marrow failure. This will allow patients to avoid the risks associated with the low blood counts of bone marrow failure, including anemia, infections and hemorrhages.

Gene Therapy Value Proposition: Early, Low-toxicity Intervention to Prevent Hematologic Failure

Source: Company data

RCKT recently presented data at the American Society of Hematology of the first four patients treated with RCKT's lentivial gene therapy for FA.

Bone Marrow Engraftment: Increasing Levels Provide Evidence of Potential Survival Advantage of Gene-Corrected FA Cells

Source: Company data

Increases of Corrected Leukocytes Support Restoration of Normal Bone Marrow Function Consistent with Mosaic Phenotype

Source: ASH 2018

Functional Correction of Bone Marrow

Source: ASGCT 2018

RCKT is a best in class gene therapy company with multiple shots on goal. During the next 12 months, data will likely emerge on many of these assets and if successful, should lead to considerable upside. This report focuses on the company's lead asset and data that has been presented to date is extremely supportive of a likely successful outcome, which would lead to considerable upside. As with all biotech investments, there are obviously significant downside risks and the worst case outcome for this stock is that it ends up at zero. However, with 5 pipeline assets in development, this risk is lower than biotech companies that are reliant upon a single driver of value.

Disclosure: I am/we are long RCKT. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it. I have no business relationship with any company whose stock is mentioned in this article.

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Zinc Finger Nuclease Technology Market Estimated to Discern 2X Expansion by 2025 – Commerce Gazette

Nucleases are the enzyme, used to cleave DNA into smaller units. Zinc-finger (ZFN) nucleases are artificial restriction enzyme used to cleave DNA into smaller fragments. It is the class of engineered DNA-binding proteins that creates double standard break at specified locations. It consist of two functional domain, a DNA-binding domain, and a DNA-cleaving domain. DNA binding domain recognizes the unique hexamer sequence of DNA and DNA-cleaving domain consisting nuclease domain of Fok I. The fusion between the DNA-binding domain, and a DNA-cleaving domain creates artificial restriction enzyme known as molecular scissor that cleaves the desired DNA sequence. ZFN is based on the DNA repair machinery and is becoming a prominent tool in the field of genome editing.

Zinc finger nucleases are useful for various biotechnological and life science applications. It is used to manipulate plants and animals for research purpose and is used in the clinical trial of CD4+ human T-cells for the treatment of AIDS. It is also used in the generation of disease model known as isogenic human disease model. The therapeutic approach involving ZFNs is associated with the problems related to viral gene delivery, ex vivo therapy involving own stem cells. Some of the disadvantages of the zinc finger nuclease technology is that sometimes cannot target the specific site, within the gene of interest and creates many double standard break and yield chromosomal rearrangements, which can lead to cell death and risk of immunological response against the therapeutic agent.

The rise in the incidence of chronic diseases such as cardiovascular diseases, cancer, blood pressure, obesity and others due to sedentary lifestyle has led to the excessive research and development for the development of new therapeutic agent to treat various disease condition. Benefits of Zinc Finger Nuclease (ZFN) includes permanent and heritable mutations, are effective for the variety of mammalian somatic cell types, single transfection is enough to induce editing in gene, antibiotic screening is not required for selection. These benefits has helped researched to carry out their research process easily with limited accessories.

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Zinc finger nuclease will be the core technology for biotechnology companies in coming years due to its wide applications such as cell screening, cell based optimization, target validation, functional genome editing to produce higher yield of target proteins, antibodies and others. Well- established, robust protocol using zinc finger nuclease technology will deliver accurate results and boost the market of zinc finger nuclease technology in the near future.

The global market zinc finger nuclease technology is segmented on basis of application, end user and geography:

Segment by Application Cell Line Engineering Animal Genetic Engineering Plant Genetic Engineering Others

Segment by End User Biotechnology Companies Pharmaceutical Companies Hospital Laboratory and Diagnostic Laboratory Academic and Research Institutes

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The global market for zinc finger nuclease technology is segmented into application type and end user. Based on the application type, the zinc finger nuclease market is segmented into cell line engineering, animal genetic engineering, plant genetic engineering, Based on the end user, the market is segmented into biotechnology industry, pharmaceutical company, hospital and diagnostic laboratory, academic and research institutes. Due to technological advantage of ZFN technology over other genome editing technologies, high precision, specificity, and efficacy of the zinc finger technology has projected to the growth of the zinc finger technology market in the near future

By regional presence, the global zinc finger nuclease technology market is segmented into five broad regions viz. North America, Latin America, Europe, Asia-Pacific, and the Middle East & Africa. North America is estimated to account for major share followed by European countries. Mainly the U.S. & European markets, owing to its innate nature of developed healthcare infrastructure, adopts advanced technology at early stage as compared to developing economies, high pricing of drugs/medical devices/technology, increase in incidence of lifestyle diseases, that follows large patient pool etc. is estimated to maintain its leadership geographically . Significant economic development has led to an increase in healthcare availability in Asia Pacific region, growing number of research institutes, laboratories, investment in research and development and penetration of global players in Asia is expected to fuel demand for gene editing technologies such as zinc finger nuclease technology for research and development, advancement in the diagnostic and treatment process.

Some of the major players in zinc finger nuclease technology are Sigma-Aldrich Co. LLC., Sangamo Therapeutics, Inc. OriGene Technologies, Inc., Labomics, Thermo Fisher Scientific, and others. Sigma-Aldrich Co. LLC is a part of Merck Inc. and operated life science business and has reached various geographies to fulfill customer needs. Sangamo Therapeutics, Inc. has developed range of gene editing technologies with therapeutic approach. Many life sciences company and large pharmaceutical company are collaborating to develop and commercialize gene editing technologies to introduce advanced life science products

The report covers exhaustive analysis on: Zinc Finger Nuclease Technology Segments Zinc Finger Nuclease Technology Dynamics Historical Actual Market Size, 2012 2016 Zinc Finger Nuclease Technology Size & Forecast 2017 to 2025 Zinc Finger Nuclease Technology Current Trends/Issues/Challenges Competition & Companies Involved Zinc Finger Nuclease Technology Drivers And Restraints

Regional analysis includes North America Latin America Europe Asia Pacific Middle East & Africa

Report Highlights: Shifting Industry dynamics In-depth market segmentation Historical, current and projected industry size Recent industry trends Key Competition landscape Strategies of key players and product offerings Potential and niche segments/regions exhibiting promising growth A neutral perspective towards market performance

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Zinc Finger Nuclease Technology Market Estimated to Discern 2X Expansion by 2025 - Commerce Gazette

Tooth Regeneration Market : Huge Growth Opportunity by Trend, Key Players and Forecast 2026 – TodayTimes

Tooth regeneration is a stem cell-based regenerative medical procedure that is used in tissue engineering and stem cell biology sectors. The tooth regeneration procedure replaces the damaged or lost tooth by growing it from autologous stem cells. Somatic cells are collected and reprogrammed to induce pluripotent stem cells and dental lamina with the help of reabsorbable biopolymer. Dental stem cells and cell-

activating cytokines are expected to be an approach for tooth tissue regeneration, as they have the potential to differentiate into tooth tissues in in vitro form and in vivo form. Tooth replacement therapy is considered to be a highly attractive concept for the next generation regenerative therapy, which is also known as bioengineered organ replacement. The usage and availability of different types of tooth regeneration has been evolving since the last century; however, further research still continues to develop its more clinical applications and reduce the adverse effect associated with the usage of tooth regeneration during surgery.

A major factor driving the tooth regeneration market is the high incidence of dental issues, witnessed globally. Rise in incidence of periodontics among young adults and the rising demand for stem cell tooth regeneration techniques, especially among the geriatric population, are a few other factors that are anticipated to drive the tooth regeneration market. Favorable reimbursement policies such as coverage of Medicaid insurance for dental loss treatment and emergence of new technologies such as laser tooth generation techniques are expected to propel the global tooth regeneration market. According to the World Health Organization, complete loss of teeth affects approximately 30% of the geriatric population between the ages of 65 and 74. However, prevalence rates are increasing in low and middle income countries. However, some factors such as preference for endodontic treatment over tooth regeneration products in major dental surgeries and local inflammatory activity, which results in chronic complications to dental replacements, is projected to restrain the market during the forecast period.

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The global tooth regeneration market can be segmented based on application, end-user, and regions. In terms of application, the tooth regeneration market can be segmented into dentin, pulp, enamel, and others. The dentin segment accounted for a prominent share of the global tooth regeneration market in 2018, due to the increasing prevalence of dental surgery and the rising demand for tooth regeneration in cosmetic surgery, especially from emerging economies such as China, Brazil, and India. In terms of end-user, the market can be segregated into hospitals, dental clinic, aesthetics, ambulatory care centers, and others.

In terms of regions, the global tooth regeneration market can be segmented into North America, Europe, Asia Pacific, Latin America, and Middle East & Africa. North America is projected to dominate the global tooth regeneration market during the forecast period due to increase in demand for dental services and stem cell research. According to the Dental health services of Canada, in 2018, the total expenditures on dental services in Canada amounted to US$ 13.6 Bn. The private sector expenditure was estimated to be US$ 12.7 Bn, while the public sector expenditure was estimated to be US$ 846 Mn. In April 2017, Unilever launched an in-clinic remineralisation regime to regenerate professionally advanced enamel serum. The brand claimed 82% of the enamel mineral regenerated after 3 days. Furthermore, the increasing prevalence of dental cavities & periodontics, especially in developing countries such as China and India has led to the increasing demand for orthopedic & dental surgery. According to World Health Organization, nearly 60% to 90% of school children and nearly 100% of adults have dental cavities. However, Asia Pacific is witnessing an increase in the incidence of dental surgery, general prosthetic fixation, periodontal inflammation, and other dental diseases. This, in turn, is anticipated to fuel the demand for cost-effective aesthetic and dental surgery. These factors are projected to drive the tooth regeneration market in Asia Pacific between 2017 and 2026.

Key players operating in the global tooth regeneration market include Unilever, Ocata Therapeutics, Integra LifeSciences, CryoLife, Inc., BioMimetic Therapeutics, Inc. (Wright Medical Group, Inc.), Cook Medical, and StemCells Inc.

The report offers a comprehensive evaluation of the market. It does so via in-depth qualitative insights, historical data, and verifiable projections about market size. The projections featured in the report have been derived using proven research methodologies and assumptions. By doing so, the research report serves as a repository of analysis and information for every facet of the market, including but not limited to: Regional markets, technology, types, and applications.

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The study is a source of reliable data on: Market segments and sub-segments Market trends and dynamics Supply and demand Market size Current trends/opportunities/challenges Competitive landscape Technological breakthroughs Value chain and stakeholder analysis

The regional analysis covers: North America (U.S. and Canada) Latin America (Mexico, Brazil, Peru, Chile, and others) Western Europe (Germany, U.K., France, Spain, Italy, Nordic countries, Belgium, Netherlands, and Luxembourg) Eastern Europe (Poland and Russia) Asia Pacific (China, India, Japan, ASEAN, Australia, and New Zealand) Middle East and Africa (GCC, Southern Africa, and North Africa)

The report has been compiled through extensive primary research (through interviews, surveys, and observations of seasoned analysts) and secondary research (which entails reputable paid sources, trade journals, and industry body databases). The report also features a complete qualitative and quantitative assessment by analyzing data gathered from industry analysts and market participants across key points in the industrys value chain.

A separate analysis of prevailing trends in the parent market, macro- and micro-economic indicators, and regulations and mandates is included under the purview of the study. By doing so, the report projects the attractiveness of each major segment over the forecast period.

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 An objective assessment of the trajectory of the market Recommendations to companies for strengthening their foothold in the market

Note:Although care has been taken to maintain the highest levels of accuracy in TMRs reports, recent market/vendor-specific changes may take time to reflect in the analysis.

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Tooth Regeneration Market : Huge Growth Opportunity by Trend, Key Players and Forecast 2026 - TodayTimes

Direct generation of human naive induced pluripotent stem …

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Direct generation of human naive induced pluripotent stem ...

Somatic Stem Cells and Cancer – Stem Cell Centers …

Can some somatic stem cells in our bodies be the source of common cancers? The Department of Health weighs in: So-called cancer stem cells are cancer cells that have stem cell-like properties, i.e., they can self-renew and differentiate into other cell types. They are associated with some, but not all, types of cancers.

Data suggest that recurrence of some cancers is caused by a failure of current therapies to target and kill these cancer stem cells. However, the relationship between cancer stem cells and somatic stem cells is unclear.

Somatic stem cells can become cancerous, but cancer stem cells do not necessarily come from somatic stem cells.

The similarities between somatic stem cells and cancer cells is so close (including the fundamental abilities to self-renew and differentiate) have led many to believe that cancers are caused by transforming mutations that happen in tissue-specific stem cells. One of the reasons this theory has been given some attention is because among all cancer cells within a particular tumor, only a very small cell fraction has the limited potential to regenerate the entire tumor cell population. Thus, these cells with stem-like properties have been termed cancer stem cells. Cancer stem cells can begin from mutation in normal somatic stem cells that stop controlling their physiological programs.

The stem cell theory of cancer proposes that among all cancerous cells, a few act as stem cells that reproduce themselves and sustain the cancer, much like normal stem cells normally renew and sustain our organs and tissues. In this view, cancer cells that are not stem cells can cause problems, but they cannot sustain an attack on our bodies over the long term, Stanford Medical said.

Over the years, there have been many theories about the origins of cancer. Truth be told, we still dont have all the answers on why some cancers come to be. However, one theory that is largely accepted postulates that: the growth of tissues and the reproduction of cells in our bodies are carefully regulated through the action of key sets of DNA instructions. When those DNA sequences are disruptedwhether through viruses, environmental causes like radiation or toxins, mutations transcription errors or inborn genetic flawscell reproduction becomes less well regulated. Eventually, those changes can produce the rapidly reproducing, self-protective and opportunistic cells that typify cancer, Stanford Medicine writes.

According to the American Cancer Society, men have a 39.66 percent chance, or one in three risk, of developing cancer over a lifetime. For women, the odds are slightly lower, at 37.65 percent.

The National Institute of Health states, Data from 2007 suggest that approximately 1.4 million men and women in the U.S. population are likely to be diagnosed with cancer and approximately 566,000 American adults are likely to die from cancer in 2008.

Stem cell transplants are commonly used today to help patients that have had blood-forming stem cells depleted after high doses of chemotherapy and/or radiation. Blood forming stem cells are a vital part of health because they grow and become varying types of blood cells that your body needs such as:

For your body to be healthy, all three blood cell types play a role.

Ideal candidates for stem cell therapy include those that are suffering from pain or dysfunction due to injury or age-related joint issues. If you are you worried that surgery, a lifelong dependency on pain medications, or a departure from your prior functionality are your only options, stem cell therapy may be for you.

Find out if you are a candidate for this revolutionary treatment by scheduling a free consultation with a stem cell therapist near you! If you have questions, or would like to know more about regenerative stem cell therapy, please call us at (877) 808-0016 or click contact us.

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Somatic Stem Cells and Cancer - Stem Cell Centers ...

Difference Between Embryonic and Somatic Stem Cells …

The key difference between embryonic and somatic stem cells is that the embryonic stem cells are pluripotent undifferentiated cells that have embryonic origin while somatic stem cells are multipotent undifferentiated cells that are of tissue and organ origin.

Stem cells are undifferentiated cells which are capable of growing into true tissues or organs. Generally, there are two major stem cell types as embryonic stem cells and adult stem cells (somatic stem cells). In the case of differentiation, embryonic stem cells can differentiate into any type of cells. In contrast, somatic stem cells can only differentiate into several tissue-specific cells. Therefore, embryonic stem cells are pluripotent while somatic stem cells are multipotent. In simple words, the ability of differentiation is high in embryonic stem cells in comparison to that of somatic stem cells.

1. Overview and Key Difference 2. What areEmbryonic Stem Cells 3. What are Somatic Stem Cells 4. Similarities BetweenEmbryonic and Somatic Stem Cells 5. Side by Side Comparison Embryonic vs Somatic Stem Cells in Tabular Form 6. Summary

Embryonic stem cells are a type of undifferentiated cells present in early stages of embryonic development. The inner cell mass of the blastocyst is made up of embryonic stem cells. These embryonic stem cells are pluripotent in nature. Thus, they can differentiate into any type of cells. The extraction of embryonic stem cells can be done from the blastocyst stage of the embryonic development for stem cell culture. Following the extraction, the cells undergo maturation and division under in vitro conditions. The embryonic stem cells are able to grow in special high nutrient media where they differentiate into the three germ layers: ectoderm, endoderm, and mesoderm.

Figure 01: Embryonic Stem Cells

In modern therapy, embryonic stem cells are valuable tools in regenerative therapy and tissue replacement following injury or disease. The diseases that use embryonic stem cell therapy at present are diabetes, neurodegenerative disorders, spinal cord, and muscular injuries.

Somatic stem cells are the stem cells present in specific tissues and organs in adults. Therefore, adult stem cells is a synonym of somatic stem cells. Thus, adult stem cells originate from mature tissues and organs. They are multipotent cells; this means they can differentiate into several types of cells, but not pluripotent like embryonic stem cells. There are different types of somatic stem cells such as hematopoietic stem cells, intestinal stem cells, endothelial stem cells, neuronal stem cells, and mesenchymal stem cells.

Figure 02: Somatic Stem Cells

During division, somatic stem cells undergo two pathways. They are symmetric division and asymmetric division. The symmetric division produces daughter cells of similar properties whereas asymmetric division produces one similar daughter cell and a different progenitor cell.

There are many uses of somatic stem cells in research. They are useful in many drug testing protocols to check the effects of particular drugs or metabolites. Moreover, somatic stem cells are useful to determine the cellular behavior of particular organs and their signaling pathways. Furthermore, scientists use somatic cells as therapy as they are able to regenerate cells when proper conditions are present.

The key difference between embryonic and somatic stem cells is their site of extraction. Blastocyst stage of the embryonic development is the site of extraction of embryonic stem cells while specific tissues are the sites of extraction of somatic stem cell. Especially, embryonic stem cells can differentiate into any type of cells. In contrast, somatic stem cells cannot differentiate into all types of cells and can only differentiate into specific types of cells based on their origin. Therefore, this is also a major difference between embryonic and somatic stem cells.

Another difference between embryonic and somatic stem cells is their cell culturing process. Cell culturing of somatic stem cells are more laborious in comparison to embryonic stem cell culture.

The below infographic presents more information on the difference between embryonic and somatic stem cells.

Stem cells are undifferentiated cells. There are two broad classes of stem cells as embryonic stem cells and somatic stem cells. In summarizing the difference between embryonic and somatic stem cells, the embryonic stem cells can differentiate into any type of cells; thus, they are pluripotent. In contrast, somatic stem cells or adult stem cells can differentiate only into specific types of cells; thus, they are multipotent. Above all, the key difference between embryonic and somatic stem cells is the site of the derivation of these cell types. Embryonic stem cells are derived from the blastocyst while somatic stem cells are derived from specific organs upon the requirement.

1. Henningson, Carl T, et al. 28. Embryonic and Adult Stem Cell Therapy.The Journal of Allergy and Clinical Immunology, U.S. National Library of Medicine, Feb. 2003, http://www.ncbi.nlm.nih.gov/pubmed/12592319.

1. Human embryonic stem cells only A : Human_embryonic_stem_cells.png: (Images: Nissim Benvenisty)derivative work: Vojtech.dostal (talk) Human_embryonic_stem_cells.png (CC BY 2.5) via Commons Wikimedia 2. Sources of new adult -cells By Murtaugh, L.C. and Kopinke, D., Pancreatic stem cells (July 11, 2008), StemBook, ed. The Stem Cell Research Community, StemBook, doi/10.3824/stembook.1.3.1, http://www.stembook.org. (CC BY 3.0) via Commons Wikimedia

Samanthi holds a B.Sc. Degree in Plant Science, M.Sc. in Molecular and Applied Microbiology, and PhD in Applied Microbiology (progressing). Her research interests include Bio-fertilizers, Plant Microbe Interactions, Molecular Microbiology, Soil Fungi, and Fungal Ecology.

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Difference Between Embryonic and Somatic Stem Cells ...

Mosaic (genetics) – Wikipedia

In genetics, a mosaic, or mosaicism, involves the presence of two or more populations of cells with different genotypes in one individual who has developed from a single fertilized egg.[1][2] Mosaicism has been reported to be present in as high as 70% of cleavage stage embryos and 90% of blastocyst-stage embryos derived from in vitro fertilization.[3]

Genetic mosaicism can result from many different mechanisms including chromosome non-disjunction, anaphase lag, and endoreplication.[3] Anaphase lagging is the most common way by which mosaicism arises in the preimplantation embryo.[3] Mosaicism can also result from a mutation in one cell during development in which the mutation is passed on to only its daughter cells. Therefore, the mutation is only going to be present in a fraction of the adult cells.[2]

Genetic mosaics may often be confused with chimerism, in which two or more genotypes arise in one individual similarly to mosaicism. However, in chimerism the two genotypes arise from the fusion of more than one fertilized zygote in the early stages of embryonic development, rather than from a mutation or chromosome loss.

Different types of mosaicism exist, such as gonadal mosaicism (restricted to the gametes) or somatic mosaicism.

Somatic mosaicism occurs when the somatic cells of the body are of more than one genotype. In the more common mosaics, different genotypes arise from a single fertilized egg cell, due to mitotic errors at first or later cleavages.

In rare cases, intersex conditions can be caused by mosaicism where some cells in the body have XX and others XY chromosomes (46, XX/XY).[4][5] In the fruit fly Drosophila melanogaster, where a fly possessing two X chromosomes is a female and a fly possessing a single X chromosome is a sterile male, a loss of an X chromosome early in embryonic development can result in sexual mosaics, or gynandropmorphs.[6][7] Likewise, a loss of the Y chromosome can result in XY/X mosaic males.[8]

The most common form of mosaicism found through prenatal diagnosis involves trisomies. Although most forms of trisomy are due to problems in meiosis and affect all cells of the organism, there are cases where the trisomy occurs in only a selection of the cells. This may be caused by a nondisjunction event in an early mitosis, resulting in a loss of a chromosome from some trisomic cells.[9] Generally this leads to a milder phenotype than in non-mosaic patients with the same disorder.

An example of this is one of the milder forms of Klinefelter syndrome, called 46/47 XY/XXY mosaic wherein some of the patient's cells contain XY chromosomes, and some contain XXY chromosomes. The 46/47 annotation indicates that the XY cells have the normal number of 46 total chromosomes, and the XXY cells have a total of 47 chromosomes.

Around 30% of Turner's syndrome cases demonstrate mosaicism, while complete monosomy (45, X) occurs in about 5060% of cases.

But mosaicism need not necessarily be deleterious. Revertant somatic mosaicism is a rare recombination event in which there is a spontaneous correction of a mutant, pathogenic allele.[10] In revertant mosaicism, the healthy tissue formed by mitotic recombination can outcompete the original, surrounding mutant cells in tissues like blood and epithelia that regenerate often.[10] In the skin disorder ichthyosis with confetti, normal skin spots appear early in life and increase in number and size over time.[10]

Other endogenous factors can also lead to mosaicism including mobile elements, DNA polymerase slippage, and unbalanced chromosomal segregation.[11] Exogenous factors include nicotine and UV radiation.[11] Somatic mosaics have been created in Drosophila using Xray treatment and the use of irradiation to induce somatic mutation has been a useful technique in the study of genetics.[12]

True mosaicism should not be mistaken for the phenomenon of Xinactivation, where all cells in an organism have the same genotype, but a different copy of the X chromosome is expressed in different cells. The latter is the case in normal (XX) female mammals, although it is not always visible from the phenotype (like it is in calico cats). However, all multicellular organisms are likely to be somatic mosaics to some extent.[13]

Somatic mutation leading to mosaicism is prevalent in the beginning and end stages of human life.[11] Somatic mosaics are common in embryogenesis due to retrotransposition of L1 and Alu transposable elements.[11] In early development, DNA from undifferentiated cell types may be more susceptible to mobile element invasion due to long, un-methylated regions in the genome.[11] Further, the accumulation of DNA copy errors and damage over a lifetime lead to greater occurrences of mosaic tissues in aging humans. As our longevity has increased dramatically over the last century, our genome may not have had time to adapt to cumulative effects of mutagenesis.[11] Thus, cancer research has shown that somatic mutations are increasingly present throughout a lifetime and are responsible for most leukemia, lymphomas, and solid tumors.[14]

Genomic mosaiscism arises in developing and in adult brain cells leading to diverse, seemingly random, genomic changes.[15] A frequent type of neuronal genomic mosaicism is copy number variation. Possible sources of such variation were suggested to be incorrect repair of DNA damages and somatic recombination.[15][16]

One basic mechanism which can produce mosaic tissue is mitotic recombination or somatic crossover. It was first discovered by Curt Stern in Drosophila in 1936. The amount of tissue which is mosaic depends on where in the tree of cell division the exchange takes place. A phenotypic character called "Twin Spot" seen in Drosophila is a result of mitotic recombination. However, it also depends on the allelic status of the genes undergoing recombination. Twin spot occurs only if the heterozygous genes are linked in repulsion i.e. trans phase. The recombination needs to occur between the centromere the adjacent gene. This gives an appearance of yellow patches on the wild type background in Drosophila. another example of mitotic recombination is the Bloom's syndrome which happens due to the mutation in the blm gene. The resulting BLM protein is defective. the defect in RecQ an helicase facilitates the defective unwinding of DNA during replication and is thus associated with the occurrence of this disease.[17][18]

Germline or gonadal mosaicism is a special form of mosaicism, where some gametesi.e., sperm or oocytescarry a mutation, but the rest are normal.[19][20]

The cause is usually a mutation that occurred in an early stem cell that gave rise to all or part of the gametes.

This can cause only some offspring to be affected, even for a dominant disease.

Genetic mosaics can be extraordinarily useful in the study of biological systems, and can be created intentionally in many model organisms in a variety of ways. They often allow for the study of genes that are important for very early events in development, making it otherwise difficult to obtain adult organisms in which later effects would be apparent. Furthermore, they can be used to determine the tissue or cell type in which a given gene is required and to determine whether a gene is cell autonomous. That is, whether or not the gene acts solely within the cell of that genotype, or if it affects the entire organism of neighboring cells which do not themselves contain that genotype.

The earliest examples of this involved transplantation experiments (technically creating chimeras) where cells from a blastula stage embryo from one genetic background are aspirated out and injected into a blastula stage embryo of a different genetic background.

Genetic mosaics are a particularly powerful tool when used in the commonly studied fruit fly, where specially-selected strains frequently lose an X[7] or a Y[8] chromosome in one of the first embryonic cell divisions. These mosaics can then be used to analyze such things as courtship behavior,[7] female sexual attraction,[21] and the autonomy or non-autonomy of particular genes.

Genetic mosaics can also be created through mitotic recombination. Such mosaics were originally created by irradiating flies heterozygous for a particular allele with X-rays, inducing double-strand DNA breaks which, when repaired, could result in a cell homozygous for one of the two alleles. After further rounds of replication, this cell would result in a patch, or "clone" of cells mutant for the allele being studied.

More recently the use of a transgene incorporated into the Drosophila genome has made the system far more flexible. The flip recombinase (or FLP) is a gene from the commonly studied yeast Saccharomyces cerevisiae which recognizes "flip recombinase target" (FRT) sites, which are short sequences of DNA, and induces recombination between them. FRT sites have been inserted transgenically near the centromere of each chromosome arm of Drosophila melanogaster. The FLP gene can then be induced selectively, commonly using either the heat shock promoter or the GAL4/UAS system. The resulting clones can be identified either negatively or positively.

In negatively marked clones the fly is transheterozygous for a gene encoding a visible marker (commonly the green fluorescent protein or GFP) and an allele of a gene to be studied (both on chromosomes bearing FRT sites). After induction of FLP expression, cells that undergo recombination will have progeny that are homozygous for either the marker or the allele being studied. Therefore, the cells that do not carry the marker (which are dark) can be identified as carrying a mutation.

It is sometimes inconvenient to use negatively marked clones, especially when generating very small patches of cells, where it is more difficult to see a dark spot on a bright background than a bright spot on a dark background. It is possible to create positively marked clones using the so-called MARCM ("mosaic analysis with a repressible cell marker", pronounced [mark-em]) system, developed by Liqun Luo, a professor at Stanford University, and his post-doc Tzumin Lee who now leads a group at Janelia Farm Research Campus. This system builds on the GAL4/UAS system, which is used to express GFP in specific cells. However a globally expressed GAL80 gene is used to repress the action of GAL4, preventing the expression of GFP. Instead of using GFP to mark the wild-type chromosome as above, GAL80 serves this purpose, so that when it is removed by mitotic recombination, GAL4 is allowed to function, and GFP turns on. This results in the cells of interest being marked brightly in a dark background.[22]

In 1929, Alfred Sturtevant studied mosaicism in Drosophila.[6] A few years later, In the 1930s, Curt Stern demonstrated that genetic recombination, normal in meiosis, can also take place in mitosis.[23][24] When it does, it results in somatic (body) mosaics. These are organisms which contain two or more genetically distinct types of tissue.[25] The term "somatic mosaicism" was used by C.W. Cotterman in 1956 in his seminal paper on antigenic variation.[11]

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Mosaic (genetics) - Wikipedia