Category Archives: Stem Cell Research

Researchers in the UK have developed a biodegradable hydrogel that could help repair the damage caused by heart attacks.

The gel is used as a binding agent to inject stem cells into the heart. These cells can then regenerate and rebuild areas where the tissue is damaged.

So far, the gel has only been tested in healthy mice. But scientists at the University of Manchester say its showing promising results and they hope it can become a key part of future regenerative treatments.

According to the World Health Organization (WHO) and the Lancet Burden of Disease, over nine million people each year die from coronary heart disease, the most common cause of heart failure, despite significant advances in heart surgery.

During a heart attack, blood and oxygen are cut off from the heart, which can cause muscle cells to die. Depending on the severity of the damage, patients can require a heart transplant - a complicated, invasive, and risky procedure.

The team at the University of Manchester is hoping the new gel technology can ultimately improve regenerative treatments and avoid heart transplants altogether.

Stem cell surgery has already been widely used to generate tissue. In Switzerland, surgeons have grown stem cells into cartilage and transplanted them into damaged knees.

However, successes with the heart have been more elusive. In the past, surgeons have tried to inject stem cells directly into the heart, but the cells have not survived.

"The challenges in injecting these cells into a beating heart is that the heart is a mechanical structure and that the cells, if they're injected alone, find it very difficult to find an anchor, said Professor James Leiper, Associate Medical Director at the British Heart Foundation, which funded the research.

This hydrogel is an exciting potential mechanism that we could use to really harness the regenerative capacity of stem cells".

The team at the University of Manchester says the gel can be safely injected into the beating heart to act as a scaffold for stem cells to grow new tissue.

The gel is made of chains of amino acids called peptides, the building blocks of proteins.

To prove it could work in a living heart, the team injected the gel with a fluorescent tag into the hearts of healthy mice.

The fluorescent tag revealed that the gel remained in the heart for two weeks, while ultrasounds and electrocardiograms showed the injection was safe.

Lead researcher Katharine King says this shows the cells can be held inside the hearts long enough for the stem cells to start growing.

"It's looking very promising, the way that it would stay there and be able to hold the cells there long enough for them to kind of integrate into the heart," she said.

The researchers now plan to trial the gel in mice straight after a heart attack, to see whether the heart cells can develop new muscle tissue and help restore the hearts ability to pump efficiently.

Only if trials on animals are successful will scientists be able to conduct further clinical studies to assess whether the gel can safely and effectively be used in humans, a process that typically takes several years.

"If the benefits are replicated in further research and then in patients, these gels could become a significant component of future treatments to repair the damage caused by heart attacks," Leiper said.

For more on this story, watch the video in the media player above.

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Scientists hope this injectable stem cell gel can repair heart attack damage and avoid transplants - Euronews

CAMBRIDGE, England & EDINBURGH, Scotland--(BUSINESS WIRE)--Axol Bioscience Ltd. (Axol), an established provider of iPSC-derived cells, media, and characterization services for life science discovery, today announced that its human induced pluripotent stem cell (iPSC)-derived ventricular cardiomyocytes have undergone comprehensive in vitro pro-arrhythmia assay (CiPA) validation. Using this assay, the cells were shown to be suitable for measuring cardiotoxicity, offering scientists a robust cardiac model for drug discovery and screening.

Axols human iPSC-derived ventricular cardiomyocytes are manufactured at scale according to strict quality control standards using ISO 9001-accredited quality management systems, providing a continuous source of cells from the same genetic background for use in multiple experiments. This offers a physiologically relevant in vitro research model of human heart cells to reliably and repeatably test drug candidates for cardiotoxicity at scale.

With the advent of human iPSC-derived cardiomyocytes, the US Federal Food and Drug Administration Agency (FDA) launched a working group to assess the utility of these cells in reproducing cardiotoxicity in a dish, known as CiPA*. The assay tests cells with 28 compounds that are known to be cardiotoxic and induce the fatal arrhythmia Torsades de Pointes. Clyde Biosciences, a CRO that specializes in cardiotoxicity assays, used this assay to validate Axols cardiomyocytes for cardiac safety testing. Using these cells could help researchers to identify unsuitable drug candidates earlier in the drug discovery process and improve the number of promising pre-clinical drug candidates that translate through to clinical trials and to patients.

Liam Taylor, CEO, Axol Bioscience, said: Scientists need cells and reagents they can rely on to make meaningful assessments of drug candidate toxicity, before progressing candidates to the clinic.

Were both excited and proud to demonstrate the suitability of our human iPSC-derived ventricular cardiomyocytes for toxicity testing. Axols stringent quality control standards mean we have the capability to produce reliable, validated cells that scientists can use to assess a compounds cardiac liability and, ultimately, help to improve the drug discovery process.

Prof. Godfrey Smith, CSO, Clyde Biosciences, added: As a core member of the CiPA initiative, were pleased to have supported Axols cell development and helped the team assess the performance of its cardiomyocytes. Having run the CiPA protocol on Clydes proprietary CellOPTIQ platform, and provided analysis and interpretation of the data, we confirm our data indicates that Axols cardiomyocytes meet the requirements for predictive in vitro pro-arrhythmia screening.

For further information about Axols human iPSC-derived cardiomyocytes, please visit: https://axolbio.com/cells/cardiovascular-system/

Dr. Jamie Bhagwan, Group Leader, Axol Bioscience will present data describing the development of Axols iPSC-derived cardiomyocytes alongside Clyde Biosciences Prof. Godfrey Smith at a free-to-attend webinar on June 9th, at 6 PM BST / 1 PM ET / 10 AM PT. Register here: https://register.gotowebinar.com/register/1085358037527496720?hss_channel=lcp-

Axol will also be attending the International Society for Stem Cell Research (ISSCR) Annual Meeting in San Francisco, USA from June 1518, 2022. Visit booth 440 to learn more.

* About CiPA: https://cipaproject.org/about-cipa/#About

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Axol Bioscience Introduces CiPA-Validated Human Stem Cell-Derived Ventricular Cardiomyocytes to Help Improve Drug Discovery - Business Wire

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Fasting sends muscle stem cells into a deep resting state that slows muscle repair but also makes them more resistant to stress, according to a study of laboratory mice.

The protective effect can also be achieved by feeding the mice high-fat, low-carbohydrate foodalso known as a ketogenic dietthat mimics how the body responds to fasting, or by giving the animals ketone bodies, the byproducts that occur when the body uses fat as an energy source.

The research explores how the body responds in times of deprivation and plenty and gives clues about the effect of aging on the ability to regenerate and repair damaged tissue. Although the study focused on muscle stem cells, the researchers believe the findings are applicable to other types of tissue throughout the body.

As we age, we experience slower and less complete healing of our tissues, says Thomas Rando, professor of neurology and neurological sciences at Stanford University. We wanted to understand what controls that regenerative ability and how fasting impacts this process. We found that fasting induces resilience in muscle stem cells so that they survive during deprivation and are available to repair muscle when nutrients are again available.

Rando, who recently accepted a position as the director of the Broad Stem Cell Research Center at UCLA, is the senior author of the study in Cell Metabolism. Instructor Daniel Benjamin and graduate student Pieter Both are the lead authors of the study.

Its been well documented that long-term caloric restriction extends the lifespan and promotes the overall health of laboratory animals, but it is difficult for people to maintain a very-low-calorie diet for months or years. Periodic fasting has been explored as another way to obtain the health benefits of caloric restriction, but the effects of intermittent fasting on the body and its ability to regenerate damaged or aging tissues have not been well studied.

Fasting or, alternatively, eating a ketogenic diet high in fat and low in carbohydratesa popular weight-loss techniquecauses the body to enter a state called ketosis, in which fat is the primary energy source. Ketone bodies are the byproducts of fat metabolism.

The researchers found that mice that had fasted between 1 and 2.5 days were less able than non-fasting animals to regenerate new muscle in their hind legs in response to injury. This reduced regenerative capacity persisted for up to three days after the mice began feeding again and returned to a normal body weight; it returned to normal within one week of the end of the fast.

Further research showed that muscle stem cells from fasting animals were smaller and divided more slowly than those from non-fasting animals. But they were also more resilient: They survived better when grown on a lab dish under challenging conditions including nutrient deprivation, exposure to cell-damaging chemicals, and radiation. They also survived transplantation back into animals better than those from non-fasting animals.

Usually, most laboratory-grown muscle stem cells die when transplanted, Rando says. But these cells are in a deep resting state we call ketone-induced deep quiescence that allows them to withstand many kinds of stress.

Muscle stem cells isolated from non-fasting animals and then treated with a ketone body called beta-hydroxybutyrate (BHB) displayed a similar resilience as did those from fasting animals, the researchers found. Additionally, muscle stem cells isolated from mice fed a ketogenic diet, or a normal diet coupled with injections of ketone bodies, displayed the same characteristics of the deeply quiescent stem cells from fasting animals.

Finally, the researchers isolated muscle stem cells from old mice that had been treated with ketone bodies for one week. Previous research in Randos lab showed that these aged muscle stem cells grew more poorly in the laboratory than muscle stem cells from younger animals. But treatment with the ketone bodies allowed the old muscle stem cells to survive as well as their younger counterparts.

Although more research needs to be done, the results are intriguing, the researchers say.

Cells evolved to exist in times of abundance and in times of deprivation, Rando says. They had to be able to survive when food was not readily available. Ketone bodies arise when the body uses fat for energy, but they also push stem cells into a quiescent state that protects them during deprivation. In this state, they are protected from environmental stress, but they are also less able to regenerate damaged tissue.

Balancing these outcomes might one day help combat normal aging and enhance stem cell function throughout the body, the researchers speculate.

It would be beneficial if the effects of fasting on stem cells could be attained through ketone bodies, supplanting the need to fast or to eat a ketogenic diet, Rando says. Perhaps it may be possible to eat normally and still get this increased resilience.

The National Institutes of Health, the Buck Institute for Research on Aging, and the Department of Veterans Affairs supported the work.

Researchers from UC Berkeley, the Veterans Affairs Palo Alto Health Care System, and the Mondor Institute for Biomedical Research in France are coauthors of the study.

Source: Stanford University

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Fasting has pros and cons for muscle repair in mice - Futurity: Research News

Leading experts among 3D printing manufacturers and regenerative medicine company 3DBio Therapeutics have successfully performed a clinical trial of transplanting a 20-year-old female's ear utilizing a 3D-printed iteration made from the same female's cells.

The doctors involved relayed key details surrounding the trial amid a press release, yet had to refrain from fully unearthing all of the secrets behind their efforts with the so-called AuriNovo ear due to proprietary concerns.

The woman treated with the 3D-printed ear implant suffered from a rare genetic birth deformity, called microtia, which either causes one or both ears to not grow at all or grow in an underdeveloped manner.

Nearly 1,500 US children are born with the condition, thus spurring 3DBio Therapeutics to enact a clinical trial involving so far a total of 11 participants with their AuriNovo ear implant.

The 3D printed ear implant relies on the client's own tissue to replace their deformed or missing ear. Usually, such patients suffering from microtia accept grafts taken from their ribs or alternative synthetic materials, but 3DBio Therapeutics does it vastly differently, as the tissue engineering and regenerative medicine company instead opts to leverage the patient's cartilage cells from the existing ear following a biopsy.

Related Article:Pig Heart Transplant Patient Dies, Cause of Death Unknown-Xenotransplantation Not Yet Effective?

From there, the team takes the cells and grows them via 3D printing technology, shaping the newly-formed product into the patient's ear.

Utilizing the patient's own cells ensures that the AuriNovo ear will be less likely to be rejected from the client. Plus, over time, the new appendage will continue regenerating throughout that particular patient's life.

"This is truly a historic moment for patients with microtia, and more broadly, for the regenerative medicine field as we are beginning to demonstrate the real-world application of next-generation tissue engineering technology," says Chief Executive Officer and co-founder of 3DBio Therapeutics, Daniel Cohen, within the press release. "It is the culmination of more than seven years of our company's focused efforts to develop a uniquely differentiated technology platform meeting the FDA's requirements for therapeutic manufacturing of reconstructive implants."

Similar advancements in the fields of tissue engineering and regenerative medicine have proven to witness astounding growth, evidenced best via a heart transplant initiated in early January of this year, wherein the patient was given a pig heart as substitute for their muscular organ.

Unfortunately, the patient would later die due to a viral pig infection, but does lend credence to the potential of 3D printed heart transplants, and continued tissue engineering efforts in line with stem cell research.

The groundbreaking achievement provided via 3DBio Therapeutics was documented in a New York Times feature, wherein both doctors voiced even more information surrounding their 3D printed ear transplant.

Of those involved in the procedure, San Antonia's pediatric ear reconstructive surgeon Dr. Arturo Bonilla offered the most heartwarming of all considerations on the future of the AuriNovo project:

"This is so exciting, sometimes I have to temper myself a little bit. If everything goes as planned, this will revolutionize the way this is done."

Read Also:Scientists Successfully 3D Print Human Corneas; This Breakthrough Can Be the Solution for Transplant Shortage

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First Clinical Trial of Transplanted 3D Ear Using Human Cells Proves Successful via 3DBio Therapeutics - Tech Times

DUBLIN--(BUSINESS WIRE)--The "Dimethyl Sulfoxide (DMSO) - Global Market Trajectory & Analytics" report has been added to ResearchAndMarkets.com's offering.

Amid the COVID-19 crisis, the global market for Dimethyl Sulfoxide (DMSO) estimated at US$226.1 Million in the year 2020, is projected to reach a revised size of US$341.7 Million by 2027, growing at a CAGR of 6.1% over the analysis period 2020-2027.

Pharmaceuticals, one of the segments analyzed in the report, is projected to grow at a 6.6% CAGR to reach US$193.4 Million by the end of the analysis period. After an early analysis of the business implications of the pandemic and its induced economic crisis, growth in the Electronics segment is readjusted to a revised 5.8% CAGR for the next 7-year period. This segment currently accounts for a 22.9% share of the global Dimethyl Sulfoxide (DMSO) market.

The U.S. Accounts for Over 19.3% of Global Market Size in 2020, While China is Forecast to Grow at a 7.3% CAGR for the Period of 2020-2027

The Dimethyl Sulfoxide (DMSO) market in the U.S. is estimated at US$43.5 Million in the year 2020. The country currently accounts for a 19.25% share in the global market. China, the world second largest economy, is forecast to reach an estimated market size of US$152.5 Million in the year 2027 trailing a CAGR of 7.3% through 2027. Among the other noteworthy geographic markets are Japan and Canada, each forecast to grow at 3.8% and 5.1% respectively over the 2020-2027 period. Within Europe, Germany is forecast to grow at approximately 4.5% CAGR while Rest of European market (as defined in the study) will reach US$152.5 Million by the year 2027.

Chemicals Segment Corners a 15.9% Share in 2020

In the global Chemicals segment, USA, Canada, Japan, China and Europe will drive the 4.8% CAGR estimated for this segment. These regional markets accounting for a combined market size of US$30 Million in the year 2020 will reach a projected size of US$41.6 Million by the close of the analysis period. China will remain among the fastest growing in this cluster of regional markets. Led by countries such as Australia, India, and South Korea, the market in Asia-Pacific is forecast to reach US$29.9 Million by the year 2027.

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Key Topics Covered:

I. METHODOLOGY

II. EXECUTIVE SUMMARY

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Insights on the Dimethyl Sulfoxide (DMSO) Global Market to 2027 - Expanding Research and Development in Stem Cell Transplantation to Benefit Demand...

As previously reported by BioSpace, a group of scientists from The Babraham Institutein the United Kingdom was able to successfully rejuvenate skin cells by a full 30 years.

The research team published a study in eLife Sciences last month describing their process of using induced pluripotent stem cell (iPSC) reprogramming to reverse aging effects at the cellular level.

Study co-author Ins Milagre told BioSpace that the research process was a team effort. In Lead Author Wolf Reiks lab, she was working on cell reprogramming while a colleague focused on the epigenetic clock.

Milagre came into her research career driven by an early interest in biology. I was fascinated by biology all of my life. I had a very good biology teacher when I was in high school, she said.

She explained that she was also a huge fan of the drama series The X-Files, seeing Gillian Anderson's character, Dana Scully, as a role model. I thought that being a scientist must be very cool. This combination made me decide to go into biology.

The research teams original hypothesis came from knowing that we can easily program cells to be zero years of age. No matter what age they are in the beginning, the cells normally reprogram back to embryonic age, or zero years of age.

Though reprogrammed embryonic cells are free of gradual aging decline, they lack identity and thus function. The research team began to consider what would happen if they could get the cells to only partially rejuvenate.

With embryonic cells, downstream applications can be a problem. We thought that maybe we could just rejuvenate the cells and then coax them back into being the cell of origin, Milagre explained. At first, the idea was casually discussed over happy hour, but then the team found that preliminary experiments yielded promising results.

They utilized Yamanaka factors (Oct4, Sox2, Klf4, c-Myc), which are typically used to differentiate cells into the embryonic stem cell stage. Instead of allowing the full time that it takes for cells to get to the embryonic life stage, we decided to stop the reprogramming process halfway through, Milagre said.

By doing this, we were able to get the cells to a younger age. They were easily reverted back to the original cell type, which in our case, were skin cells. Pausing the process in the middle allowed the cells to become a younger version of the same cell type. The researchers named the novel method maturation phase transient reprogramming (MPTR).

What I find very exciting about this study is that we showed that it's possible to rejuvenate cells, she said. Though the Yamanaka factors have been used in other labs, the Babraham Institute team was the first to rejuvenate cells by a full 30 years.

Courtesy ofFtima Santos

The scientists observed several benefits of the functionally younger cells. The skin cells were better able to produce collagen, and they were responding better to wound healing sites, Milagre said. The above photo depicts the collagen levels of the skin cells before and after rejuvenation. On the left are the original 53-year-old skin cells, and on the right are the reprogrammed cells. The collagen levels are depicted in red.

Milagre noted that the study is very preliminary, with much more research to be completed before the technology is safe and available. We only tested this in skin cells, so we don't know if this is also possible in other cell types, though we believe that it probably is based on similar work from other groups.

Another element that must be studied is how the technology will work without using the same viral vectors. We need to make a safer technology to do this. As a proof of principle, we showed that it's possible to rejuvenate cells by 30 years. Now, we need to do more research to be able to eventually move this technology into a more clinical setting.

Once the technology is safe and ready, Milagre noted that many downstream applications could be possible. We can think about trying to tackle neurodegenerative and degenerative disorders as well as ameliorating some aging effects. If we can get cells to be functionally younger, even if we don't expand peoples lives, we might be able to give people a better quality of life.

Reik explained in an earlier article that the findings could eventually lead to targeting specific genes that would be able to rejuvenate without any reprogramming. Milagre said that Yamanaka factors are working as pioneers that can start new gene expression programs. If we understand which genes are being activated downstream, we can eventually think about modulating these genes. We can try switching on a minimum number of effector genes. This would be a way to overcome using viral vectors.

Though potential future benefits of the findings are a long way off, the team is still considering the people they may help down the line. We hope the technology will help people live better lives without diseases, or without the consequences of a disease even if they still have it, Milagre said.

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Scientists Rejuvenate Skin Cells by 30 Years, with Pioneering Potential - BioSpace

Medi-Tech Insights

Increasing prevalence of HIV/AIDS and cancer, growing focus on immunology and immuno-oncology research, advent of AI platforms in flow cytometry workflows, increase in R&D investment to develop multicolor assays and advanced reagents are the key driving factors. However, high cost of flow cytometry products is still a major constraint for the Flow Cytometry market growth.

Brussels, Belgium, May 09, 2022 (GLOBE NEWSWIRE) --

Flow Cytometry is a technique used to detect and measure physical and chemical characteristics of a population of cells or particles usually suspended in a fluid using a laser beam. Most common types of flow cytometry-based proliferation assays are cell-based and bead-based assays.

Growing Adoption of Flow Cytometry in Stem Cell Research

Flow cytometry and cell sorting are critical tools in stem cell research. Recent advances in flow cytometric hardware, reagents, software platforms and algorithms have synergized to permit the stem cell biologist in better identifying and isolating rare cells based on their immunofluorescence and light scattering characteristics. By multiple fluorescent-labeled antibodies, researchers can obtain robust data and population-based statistics on differentiating stem cell cultures. The growing market penetration in stem cell research, adoption of recombinant DNA technology for antibody production, and evolution of tandem flow cytometry technologies is expected to open growth opportunities in the market.

Flow Cytometry is turning researchers into molecular detectives and helping them to delve into the depths of diseases. It allows researchers and scientists to probe the more complex and transient cellular changes that underpin the course of disease and responses to treatment, helping them better select the right drug target. - Senior Director, Data Sciences & Quantitative Biology, Pharmaceutical & Biotechnology Company, US

Rise in Chronic Diseases Increases Flow Cytometry Utilization

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Rising prevalence of chronic diseases such as cancer, hematological malignancies etc. is fueling the growth of the flow cytometry market. Flow cytometry is considered an efficient tool for clinical diagnosis of these diseases. Growing preference by health specialists to use allergenic and autologous stem cell therapies instead of radiation and chemotherapies is another key factor driving the flow cytometry market.

North America Leads in terms of Adoption of Flow Cytometry Market

North America dominates the global flow cytometry market with >40% share, followed by Europe. Growing research activities, well-established infrastructure and rising drug discovery development are the key driving factors.

Competitive Landscape: Flow Cytometry Market

The prominent players operating in the flow cytometry market are BD, Danaher Corporation, Luminex Corporation, Bio-Rad Laboratories, Apogee Flow Systems, among others.

Explore Detailed Insights on Global Flow Cytometry Market @ https://meditechinsights.com/flow-cytometry-market/

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Global Flow Cytometry Market is expected to grow at a lucrative rate of 8% to reach $11 billion by 2026 A Robust Tool that Defines New Era for...

DUBLIN--(BUSINESS WIRE)--The "Mesenchymal Stem Cells Market Research Report by Type (Allogeneic and Autologous), Indication, Source of Isolation, Application, Region (Americas, Asia-Pacific, and Europe, Middle East & Africa) - Global Forecast to 2027 - Cumulative Impact of COVID-19" report has been added to ResearchAndMarkets.com's offering.

The Global Mesenchymal Stem Cells Market size was estimated at USD 2,415.13 million in 2020, USD 2,731.51 million in 2021, and is projected to grow at a Compound Annual Growth Rate (CAGR) of 13.46% to reach USD 5,847.88 million by 2027.

Competitive Strategic Window:

The Competitive Strategic Window analyses the competitive landscape in terms of markets, applications, and geographies to help the vendor define an alignment or fit between their capabilities and opportunities for future growth prospects. It describes the optimal or favorable fit for the vendors to adopt successive merger and acquisition strategies, geography expansion, research & development, and new product introduction strategies to execute further business expansion and growth during a forecast period.

FPNV Positioning Matrix:

The FPNV Positioning Matrix evaluates and categorizes the vendors in the Mesenchymal Stem Cells Market based on Business Strategy (Business Growth, Industry Coverage, Financial Viability, and Channel Support) and Product Satisfaction (Value for Money, Ease of Use, Product Features, and Customer Support) that aids businesses in better decision making and understanding the competitive landscape.

Market Share Analysis:

The Market Share Analysis offers the analysis of vendors considering their contribution to the overall market. It provides the idea of its revenue generation into the overall market compared to other vendors in the space. It provides insights into how vendors are performing in terms of revenue generation and customer base compared to others. Knowing market share offers an idea of the size and competitiveness of the vendors for the base year. It reveals the market characteristics in terms of accumulation, fragmentation, dominance, and amalgamation traits.

The report provides insights on the following pointers:

1. Market Penetration: Provides comprehensive information on the market offered by the key players

2. Market Development: Provides in-depth information about lucrative emerging markets and analyze penetration across mature segments of the markets

3. Market Diversification: Provides detailed information about new product launches, untapped geographies, recent developments, and investments

4. Competitive Assessment & Intelligence: Provides an exhaustive assessment of market shares, strategies, products, certification, regulatory approvals, patent landscape, and manufacturing capabilities of the leading players

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The report answers questions such as:

1. What is the market size and forecast of the Global Mesenchymal Stem Cells Market?

2. What are the inhibiting factors and impact of COVID-19 shaping the Global Mesenchymal Stem Cells Market during the forecast period?

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4. What is the competitive strategic window for opportunities in the Global Mesenchymal Stem Cells Market?

5. What are the technology trends and regulatory frameworks in the Global Mesenchymal Stem Cells Market?

6. What is the market share of the leading vendors in the Global Mesenchymal Stem Cells Market?

7. What modes and strategic moves are considered suitable for entering the Global Mesenchymal Stem Cells Market?

Market Dynamics

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Opportunities

Challenges

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For more information about this report visit https://www.researchandmarkets.com/r/lth0os

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Global Mesenchymal Stem Cells Market Research Report to 2027 - Featuring Astellas Pharma, Axol Biosciences and BrainStorm Cell Therapeutics Among...

Paper Title: Identification of a retinoic acid-dependent hemogenic endothelial progenitor from human pluripotent stem cells

Journal: Nature Cell Biology

Authors:Christopher Sturgeon, PhD, Associate Professor of Cell, Developmental & Regenerative Biology and Medicine, Hematology & Medical Oncology in the Black Family Stem Cell Institute at the Icahn School of Medicine at Mount Sinai, and other coauthors.

Bottom Line:Blood-forming stem cells found in bone marrow are the life-saving component used in bone marrow transplants. However, suitable donors often cannot be found in many cases. This study reveals how the human embryo develops the precursor to blood forming stem cells, which researchers say can be used in the novel method they developed to generate blood-forming stem cells from cells in tissue culture.

The studyled by researchers from Mount Sinai and the San Raffaele Telethon Institute for Gene Therapy in Milan Italyconfirms many aspects of cell development, including origins and regulation, which are known to occur within both the mouse and human embryo. In the mammalian embryo, blood-forming stem cells emerge from a specialized cell type called hemogenic endothelium. These cells develop in response to a critical signal pathway known as retinoic acid, which is essential for growth. Their analysis found that stem cell populations derived from human pluripotent stem cells were transcriptionally similar to cells in the early human embryo.

Results: For years, researchers in the field of regenerative medicine have been able to obtain hemogenic endothelium from embryonic stem cells, but these cells do not produce blood-forming stem cells. In the embryo, blood-forming stem cell development requires signaling by retinoic acid.But, current state-of-the-art methods for deriving blood progenitors from human pluripotent stem cells do so in the absence of retinoic acid. In this latest study, researchers examined the dependence on retinoic acid in early cell types derived from human pluripotent stem cells. They performed single cell RNA sequencing of stem cells in vitro to better understand patterns of mesodermal cell types during early development. The research team identified a new strategy to obtain cells that are transcriptionally similar to those hemogenic endothelial cells found in the human embryo by stimulating a very discrete original population with retinoic acid.

Why the Research Is Interesting:This new method brings researchers and scientists closer to developing blood-forming stem cells in tissue culture, but also provides a pathway to establishing specialized blood cell types for transfusions and other treatments for cancer since the new method makings it possible to obtain the same original cells in adult blood that are found in a developing embryo.

Said Mount Sinai's Dr. Christopher Sturgeon of the research:We have made a major breakthrough in our ability to direct the development of stem cells in a tissue culture dish into cells that have the same gene expression signature as the immediate progenitor of a blood-forming stem cell found in the developing embryo. With this, now we can focus our efforts at understanding how to capture embryonic blood-forming stem cells, with the goal of using them as a substitute for bone marrow.

Researchers from the Washington University School of Medicine in St. Louis, MO contributed to this study.

###

To request a full copy of the paper or to schedule an interview with the researcher, please contact the Mount Sinai Press Office at stacy.anderson@mountsinai.org or 347-346-3390.

Nature Cell Biology

28-Apr-2022

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Researchers share insights about the mechanisms of human embryo and create method to develop transcriptionally similar cells in tissue culture -...

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A miniature replica of a heart chamber built from a combination of nanoengineered parts and human heart tissue offers a new way to study the heart.

Theres no safe way to get a close-up view of the human heart as it goes about its work: you cant just pop it out, take a look, then slot it back in.

Scientists have tried different ways to get around this fundamental problem: theyve hooked up cadaver hearts to machines to make them pump again, attached lab-grown heart tissues to springs to watch them expand and contract. Each approach has its flaws: reanimated hearts can only beat for a few hours; springs cant replicate the forces at work on the real muscle.

But getting a better understanding of this vital organ is urgent. In America, someone dies of heart disease every 36 seconds, according to the Centers for Disease Control and Prevention.

The new miniature replica of a heart chamber has no springs or external power sourceslike the real thing, it just beats by itself, driven by the live heart tissue grown from stem cells. The device could give researchers a more accurate view of how the organ works, allowing them to track how the heart grows in the embryo, study the impact of disease, and test the potential effectiveness and side effects of new treatmentsall at zero risk to patients and without leaving a lab.

The team behind the gadgetnicknamed miniPUMP, and officially known as the cardiac miniaturized Precision-enabled Unidirectional Microfluidic Pumpsays the technology could also pave the way for building lab-based versions of other organs, from lungs to kidneys.

We can study disease progression in a way that hasnt been possible before, says Alice White, a professor and chair of mechanical engineering at the Boston University College of Engineering. We chose to work on heart tissue because of its particularly complicated mechanics, but we showed that, when you take nanotechnology and marry it with tissue engineering, theres potential for replicating this for multiple organs.

The device could eventually speed up the drug development process, making it faster and cheaper, the researchers say. Instead of spending millionsand possibly decadesmoving a medicinal drug through the development pipeline only to see it fall at the final hurdle when tested in people, researchers could use the miniPUMP at the outset to better predict success or failure.

The project is part of CELL-MET, a multi-institutional National Science Foundation Engineering Research Center in Cellular Metamaterials thats led by Boston University. The centers goal is to regenerate diseased human heart tissue, building a community of scientists and industry experts to test new drugs and create artificial implantable patches for hearts damaged by heart attacks or disease.

Heart disease is the number one cause of death in the United States, touching all of us, says White. Today, there is no cure for a heart attack. The vision of CELL-MET is to change this.

Theres a lot that can go wrong with your heart. When its firing properly on all four cylinders, the hearts two top and two bottom chambers keep your blood flowing so that oxygen-rich blood circulates and feeds your body. But when disease strikes, the arteries that carry blood away from your heart can narrow or become blocked, valves can leak or malfunction, the heart muscle can thin or thicken, or electrical signals can short, causing too manyor too fewbeats. Unchecked, heart disease can lead to discomfortlike breathlessness, fatigue, swelling, and chest painand, for many, death.

The heart experiences complex forces as it pumps blood through our bodies, says Christopher Chen, professor of biomedical engineering. And while we know that heart muscle changes for the worse in response to abnormal forcesfor example, due to high blood pressure or valve diseaseit has been difficult to mimic and study these disease processes. This is why we wanted to build a miniaturized heart chamber.

At just 3 square centimeters, the miniPUMP isnt much bigger than a postage stamp. Built to act like a human heart ventricleor muscular lower chamberits custom-made components are fitted onto a thin piece of 3D-printed plastic. There are miniature acrylic valves, opening and closing to control the flow of liquidwater, in this case, rather than bloodand small tubes, funneling that fluid just like arteries and veins. And beating away in one corner, the muscle cells that make heart tissue contract, cardiomyocytes, made using stem cell technology.

Theyre generated using induced pluripotent stem cells, says Christos Michas, a postdoctoral researcher who designed and led the development of the miniPUMP as part of his PhD thesis.

To make the cardiomyocyte, researchers take a cell from an adultit could be a skin cell, blood cell, or just about any other cellreprogram it into an embryonic-like stem cell, then transform that into the heart cell.

In addition to giving the device literal heart, Michas says the cardiomyocytes also give the system enormous potential in helping pioneer personalized medicines. Researchers could place a diseased tissue in the device, for instance, then test a drug on that tissue and watch to see how its pumping ability is affected.

With this system, if I take cells from you, I can see how the drug would react in you, because these are your cells, says Michas. This system replicates better some of the function of the heart, but at the same time, gives us the flexibility of having different humans that it replicates. Its a more predictive model to see what would happen in humanswithout actually getting into humans.

That could allow scientists to assess a new heart disease drugs chances of success long before heading into clinical trials, Michas says. Many drug candidates fail because of their adverse side effects.

At the very beginning, when were still playing with cells, we can introduce these devices and have more accurate predictions of what will happen in clinical trials. It will also mean that the drugs might have fewer side effects.

One of the key parts of the miniPUMP is an acrylic scaffold that supports, and moves with, the heart tissue as it contracts. A series of superfine concentric spiralsthinner than a human hairconnected by horizontal rings, the scaffold looks like an artsy piston. Its an essential piece of the puzzle, giving structure to the heart cellswhich would just be a formless blob without itbut not exerting any active force on them.

We dont think previous methods of studying heart tissue capture the way the muscle would respond in your body, says Chen, whos also director of Boston Universitys Biological Design Center and an associate faculty member at Harvard Universitys Wyss Institute for Biologically Inspired Engineering. This gives us the first opportunity to build something that mechanically is more similar to what we think the heart is actually experiencingits a big step forward.

To print each of the tiny components, the team used a process called two-photon direct laser writinga more precise version of 3D printing. When light is beamed into a liquid resin, the areas it touches turn solid; because the light can be aimed with such accuracyfocused to a tiny spotmany of the components in the miniPUMP are measured in microns, smaller than a dust particle.

The decision to make the pump so small, rather than life-size or larger, was deliberate and is crucial to its functioning.

The structural elements are so fine that things that would ordinarily be stiff are flexible, says White. By analogy, think about optical fiber: a glass window is very stiff, but you can wrap a glass optical fiber around your finger. Acrylic can be very stiff, but at the scale involved in the miniPUMP, the acrylic scaffold is able to be compressed by the beating cardiomyocytes.

The pumps scale shows that with finer printing architectures, you might be able to create more complex organizations of cells than we thought was possible before, Chen says.

At the moment, when researchers try to create cells, he says, whether heart cells or liver cells, theyre all disorganizedto get structure, you have to cross your fingers and hope the cells create something. That means the tissue scaffolding pioneered in the miniPUMP has big potential implications beyond the heart, laying the foundation for other organs-on-a-chip, from kidneys to lungs.

An electrical and computer engineering student as an undergraduate, Michas says hed never seen cells in my life before starting this project. Now, hes preparing to start a new position with Seattle-based biotech Curi Bio, a company that combines stem cell technology, tissue biosystems, and artificial intelligence to power the development of drugs and therapeutics.

Christos is someone who understands the biology, says White, can do the cell differentiation and tissue manipulation, but also understands nanotechnology and whats required, in an engineering way, to fabricate the structure.

The next immediate goal for the miniPUMP team? To refine the technology. They also plan to test ways to manufacture the device without compromising its reliability.

There are so many research applications, says Chen. In addition to giving us access to human heart muscle for studying disease and pathology, this work paves the way to making heart patches that could ultimately be for someone who had a defect in their current heart.

The study is published in Science Advances. Additional coauthors are from Florida International University and Boston University.

Source: Andrew Thurston for Boston University

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