TAIPEI--(BUSINESS WIRE)--PharmaEssentia Corporation (TPEx:6446), a global biopharmaceutical innovator based in Taiwan leveraging deep expertise and proven scientific principles to deliver new biologics in hematology and oncology, today announced a series of data presentations will illustrate outcomes with ropeginterferon alfa-2b (marketed as BESREMi) among adults with polycythemia vera (PV) during the European Hematology Associations Hybrid Congress (EHA2022), June 9-17 in Vienna, Austria.

Ongoing evaluations of ropeginterferon alfa-2b expand the depth and duration of data on this innovative therapeutic supporting its ability to control the effects of polycythemia vera (PV), said Albert Qin, MD, PhD, Chief Medical Officer, PharmaEssentia. We believe these important new data offer greater clarity and confidence to physicians that this therapeutic tool represents an approach to effectively and durably treat PV.

Ropeginterferon alfa-2b presentations during EHA2022 will include:

The data presentation regarding the final results of studies leading to marketing authorization of BESREMi in Europe are a result of clinical development work of AOP Health, Vienna. PharmaEssentia has licensed ropeginterferon alfa-2b in Europe to AOP.

About Polycythemia Vera

Polycythemia Vera (PV) is a cancer originating from a disease-initiating stem cell in the bone marrow resulting in a chronic increase of red blood cells, white blood cells, and platelets. PV may result in cardiovascular complications such as thrombosis and embolism, and often transforms to secondary myelofibrosis or leukemia. While the molecular mechanism underlying PV is still subject of intense research, current results point to a set of acquired mutations, the most important being a mutant form of JAK2.1

About BESREMi (ropeginterferon alfa-2b)

BESREMi is an innovative monopegylated, long-acting interferon. With its unique pegylation technology, BESREMi has a long duration of activity in the body and is aimed to be administered once every two weeks (or every four weeks with hematological stability for at least one year), allowing flexible dosing that helps meet the individual needs of patients.

BESREMi has orphan drug designation for treatment of polycythemia vera (PV) in adults in the United States. The product was approved by the European Medicines Agency (EMA) in 2019, in the United States in 2021, and has recently received approval in Taiwan and South Korea. The drug candidate was invented by PharmaEssentia and is manufactured in the companys Taichung plant, which was cGMP certified by TFDA in 2017 and by EMA in January 2018. PharmaEssentia retains full global intellectual property rights for the product in all indications.

BESREMi was approved with a boxed warning for risk of serious disorders including aggravation of neuropsychiatric, autoimmune, ischemic and infectious disorders.

About PharmaEssentia

PharmaEssentia Corporation (TPEx: 6446), based in Taipei, Taiwan, is a rapidly growing biopharmaceutical innovator. Leveraging deep expertise and proven scientific principles, the company aims to deliver effective new biologics for challenging diseases in the areas of hematology and oncology, with one approved product and a diversifying pipeline. Founded in 2003 by a team of Taiwanese-American executives and renowned scientists from U.S. biotechnology and pharmaceutical companies, today the company is expanding its global presence with operations in the U.S., Japan, China, and Korea, along with a world-class biologics production facility in Taichung. For more information, visit our website.

1 Cerquozzi S, Tefferi A. Blast Transformation and Fibrotic Progression in Polycythemia Vera and Essential Thrombocythemia: A Literature Review of Incidence and Risk Factors. Blood Cancer Journal (2015) 5, e366; doi:10.1038/bcj.2015.95.

2022 PharmaEssentia Corporation. All rights reserved.

BESREMi and PharmaEssentia are registered trademarks of PharmaEssentia Corporation, and the PharmaEssentia logo is a trademark of PharmaEssentia Corporation.

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Umoja Biopharma, Inc.

Partnership combines Umojas technologies in gene-edited iPSCs and immune differentiation for persistent anti-tumor activity with TreeFrog Therapeutics biomimetic platform for the mass-production of iPSC-derived cell therapies in large-scale bioreactors

Umoja Biopharma and TreeFrog Therapeutics Announce Collaboration to Address Current Challenges Facing Ex Vivo Allogeneic Therapies in Immuno-Oncology

Mass-production of human induced pluripotent stem cells in a 10L bioreactor using TreeFrog Therapeutics C-Stem technology. Photo credits: TreeFrog Therapeutics

SEATTLE and PESSAC, France, June 10, 2022 (GLOBE NEWSWIRE) -- Umoja Biopharma, Inc., an immuno-oncology company pioneering off-the-shelf, integrated therapeutics that reprogram immune cells to treat patients with solid and hematologic malignancies, and TreeFrog Therapeutics, a biotechnology company aimed at making safer, more efficient and more affordable cell therapies based on induced pluripotent stem cells (iPSCs), announced today that they have entered into a collaboration to evaluate Umojas iPSC platform within TreeFrogs C-Stem technology for scalable expansion and immune cell differentiation in bioreactors.

Together, the successful pairing of Umojas RACR engineered iPS cells and TreeFrogs C-Stem technology could overcome several challenges facing ex vivo allogeneic therapies, said Ryan Larson, Ph.D., Vice President and Head of Translational Science at Umoja. Two major industry-wide challenges include the ability to scale iPSC-based culture while maintaining cell health, quality, and efficient immune cell differentiation. TreeFrogs biomimetic C-Stem technology is the perfect complementary development platform for our RACR technology, a pairing which could result in controlled, efficient iPSC expansion and differentiation into immune cells, with improved yields and quality. In addition to enhancing the differentiation and yield of immune cells within the manufacturing process, our RACR system should bring therapeutic benefit to patients, allowing for safe in vivo engraftment and persistence of tumor-killing cells without requirements for toxic lymphodepleting chemotherapy.

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Umoja is developing an engineered iPSC platform that addressesmany challenges associated with ex vivo cell therapy manufacturing, including limited scalability and manufacturing complexity.Umojas iPSCs are engineered with a synthetic rapamycin-activated cytokine receptor (RACR) to drive differentiation to, and expansion of innate cytotoxic lymphoid cells, including but not limited to natural killer (NK) cells in the absence of exogenous cytokines and feeder cells. TreeFrogs proprietary C-Stem technology relies on the high-throughput encapsulation (>1,000 capsules/second) of hiPSCs within biomimetic alginate shells, which promote in vivo-like exponential growth and protect cells from external stress. In 2021, C-Stem was demonstrated to allow for unprecedented iPSC expansion in 10L bioreactors, while preserving stem cell quality. Also enabling direct in-capsule iPSC differentiation, C-Stem constitutes a scalable, end-to-end, and GMP-compatible manufacturing platform for iPSC-derived cell therapies.

Frdric Desdouits, Ph.D., Chief Executive Officer at TreeFrog added, Our primary goal is to bring the benefits of the C-Stem technology to patients as fast as possible, either through in-house programs or strategic alliances with cell therapy leaders. Partnering with Umoja is an important step forward in immuno-oncology. Besides scale-up and cell quality, the in vivo persistence of allogeneic therapies remains a critical challenge in the industry. We believe Umojas platform will allow for safer and more efficient allogeneic cell therapies in immuno-oncology. We look forward to rapidly advancing this joint approach to clinic and contributing to the future of off-the-shelf cancer treatments.

About Umoja BiopharmaUmoja Biopharma, Inc. is an early clinical-stage company advancing an entirely new approach to immunotherapy. Umoja Biopharma, Inc. is a transformative multi-platform immuno-oncology company founded with the goal of creating curative treatments for solid and hematological malignancies by reprogramming immune cells in vivo to target and fight cancer. Founded based on pioneering work performed at Seattle Childrens Research Institute and Purdue University, Umojas novel approach is powered by integrated cellular immunotherapy technologies including the VivoVec in vivo delivery platform, the RACR/CAR in vivo cell expansion/control platform, and the TumorTag targeting platform. Designed from the ground up to work together, these platforms are being developed to create and harness a powerful immune response in the body to directly, safely, and controllably attack cancer. Umoja believes that its approach can provide broader access to the most advanced immunotherapies and enable more patients to live better, fuller lives. To learn more, visithttp://umoja-biopharma.com/.

About TreeFrog TherapeuticsTreeFrog Therapeutics is a French-based biotech company aiming to unlock access to cell therapies for millions of patients. TreeFrog Therapeutics is developing a pipeline of therapeutic candidates using proprietary C-Stem technology, allowing for the mass production of induced pluripotent stem cells and their differentiation into ready-to-transplant microtissues with unprecedented scalability and cell quality. Bringing together over 80 biophysicists, cell biologists and bioproduction engineers, TreeFrog Therapeutics raised $82M over the past 3 years to advance its pipeline in regenerative medicine and immuno-oncology. The company is currently opening technological hubs in Boston, USA, and Kobe, Japan, to drive the adoption of C-Stem and build strategic alliances with leading academic, biotech and industry players in the field of cell therapy.

Umoja Biopharma Media Contact:Darren Opland, Ph.D.LifeSci Communicationsdarren@lifescicomms.com

TreeFrog Therapeutics Media Contact:Pierre-Emmanuel GaultierTreeFrog Therapeuticspierre@treefrog.fr

A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/012ae87d-b7c6-4fa2-81dc-c769877b182c

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Robotic innovations are accelerating at a startling rate, with the development of our humanoid counterparts taking sometimes hitting very close to the real thing. Consequently, the integration of these human-like robots into our society is a priority for many research groups across the globe. Now, a research team from Tokyo University has brought us even closer to this goal by growing human skin on a robotic skeleton to create a biohybrid robot.

The development of robots made to look like humans has sparked a fiery debate in research circles, prompting some to call for a clearer line between inanimate machines and autonomous robots. To illustrate this distinction, picture a ceiling fan whirling around at a constant speed when turned on manually this is an automated machine. But when we add a temperature sensor and a processor capable of storing user preferences and environmental data, the fan can then avoid obstructions and function autonomously based on the local temperature. The machine becomes an intelligent robot attuned to its environment a first step towards becoming more human.

At present, engineers are taking this premise even further, working on robots that have more and more in common with humans. If robots do become human-like, they could become widely used in any number of applications, but developing robots that feel like humans do isnt an easy feat.

The authors of a new study explain that blurring the line between humans and robots is one of the top priorities for humanoids tasked to interact with humans. But, presently, silicone skin used in robotics falls short when it comes to the delicate textures and expressions perceived by the human derma and underlying muscles. Additionally, synthetic skin cant heal, with patches or a silicone sealant used to repair rather than regenerate worn or torn areas.

To overcome this challenge, researchers have fashioned living skin sheets that can bond to the robots frames. However, conforming these biological coverings to the frameworks uneven surfaces and sharp, dynamic joints has proven extremely challenging. It got even worse when the humanoid moves the 3-dimensional (3D) metal chassis and joints damage the skin even further, causing gross failure.

So a new solution was needed. In the new study, the team cleared this hurdle using a novel technique that can grow living human skin onto a three-jointed robotic finger. The human-like skin consists of living cells and an extracellular matrix-a 3d support system holding cells in place-exhibiting self-healing properties while allowing the jointed structure underneath to move freely.

Our goal is to develop robots that are truly human-like, first author Professor Shoji Takeuchi, from the University of Tokyo, told ZME Science in an email. The silicone rubber covers that are commonly used today may look real from a distance or in photos or videos, but when you actually get up close, you realize that it is artificial. We think that the only way to achieve an appearance that can be mistaken for a human being is to cover it with the same material as a human being, i.e., living cells. Using cells would also allow the robot to work with the excellent biological functions of skin, such as its ability to self-repair.

To fashion the biohybrid robotic finger, the team first assembled the framework and coated it with parylene, a polymer used to protect implanted medical devices from moisture and contamination in the body. Similarly, the coating prevented any toxic materials in the robotic skeleton from leaching into the human skin equivalent and damaging it.

After this, they engineered a living dermis (the middle layer of skin responsible for protecting the human body from the outside world) that can feel different sensations and produce sweat. Once this was done, they then seeded the epidermis (the outermost layer of skin in the human body that protects against foreign substances and excessive water loss).

Expanding on this, the team explains that they placed the coated robotic finger in an outsized mold to engineer the dermis. Inside the mold, there was a solution of collagen and human dermal fibroblasts, the two main components that make up this connective tissue in the human body. To ensure the dermis was seeded correctly, the framework was cultured for 14 days, and an anchor was attached to the fingers base.

Takeuchi explains how the studys success hinges on this anchor because the collagen naturally shrinks, covering the robotic substructure tightly. Conversely, if there were no anchor at the base of the finger, the collagen would contract, retreating up the stem of the robotic digit. Like a primer, the dermis equivalent provided a uniform foundation for the next coat of cells (called keratinocytes) to form the epidermis.

This time, enough room was left in the mold to form a cap at the top of the structure to add extra tensile strength to the materials, enabling a uniform thickness of living skin across the frame. Results showed that this cap prevented damage to the human-like skin once the finger and joints were in motion.

One particular difficulty was culturing the skin to match its three-dimensional aspect. We found that we could adapt the skin to the curved 3D surface shape by culturing it on site, rather than making it elsewhere and attaching to the surface. By installing an appropriate anchor structure, the entire surface could be covered, Takeuchi told ZME Science.

This method can be used to cover the 3D surface of a robotic finger while controlling tissue shrinkage through anchor fixation. In addition, multidirectional seeding of keratinocytes enables us to uniformly form the epidermis layer, the team stated in their paper.

When testing the human-skin equivalent for tensile strength and water resistance, these layers produced a skin-like texture possessing moisture-retaining properties. Additionally, the biohybrid structure had enough strength and elasticity to allow curling and stretching movements and could handle electrostatically charged polystyrene foam packing balls when allocated a task.

The team also used a skin graft technique to evaluate their skins self-healing properties. To accomplish this, they cut a hole in the biohybrid fingers skin and applied a collagen bandage to the wound. Subsequently, this patch was integrated with the human-like skin to withstand continuous movement.

Despite these promising results, the group cautioned that their crafted skin is much weaker than human skin, and they dont expect this robot human-skin-equivalent to survive for very long. The team now plans to incorporate more biological structures into their skin to address these issues, such as sensory neurons, hair follicles, nails, and sweat glands.

Speaking to ZME Science about their results overall, Takeuchi concludes that It was exciting to find that a robotic finger, completely covered with skin, could stretch and contract when it moved, without breaking, and that it could repair itself by cell proliferation when damaged. We believe this is a great step toward a new biohybrid robot with the superior functions of living organisms.

The study is published in the journalMatter.

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Without CO2 incubators, there would be no coronavirus vaccines today. They are also absolutely essential for cancer research. These multiple uses help save lives and cure many different diseases. We would now like to introduce you to some of the interesting facets of CO2 incubators.

Sponsored by BINDER GmbH.

CO2 incubators are being used to conduct research in laboratories across the globe. The Bioscience Institute Middle East, which is among the worlds leading centers for regenerative medicine, is also using an incubator to process the bodys own cells as well as for plastic surgery applications.

The cellswhich are multiplied in an incubatorare also used in tissue repair as well as for orthopedic and dermatological treatments. The Bioscience Institute only uses skin and fat tissue specimens from adult (mature) cells. Using the bodys owni.e., autologouscells eliminates the risk of rejection while also preventing the complication of graft-versus-host disease (an unwanted reaction of the donors immune cells).

To be even more specific: the CO2 incubators are predominantly used to incubate stem cells from mesenchyme tissue (undifferentiated connective tissue).

Here is how it works: first, cells are extracted from fat tissue. This process is performed by means of enzymatic disaggregation (separation) using various steps of filtration and centrifugation. The crucial stage here is the expansion, i.e., extracting as many stem cells as possible, which is why it is absolutely essential to create the best possible growth conditions.

Dr. Simona Alfano, a biologist at the Bioscience Institute, explained:

When incubating the cells, it is vitally important for the selected parameters to remain exactly constant across all levels.

And this is precisely where the CO2 chambers from BINDER come into their ownwith their reproducible growth conditions, constant climatic conditions, low risk of contamination and high level of safety.

Find out more about why the ph value is a key factor in cell and tissue cultures.

CO2 chambers also played an important role during the coronavirus pandemic: firstly, in the development of coronavirus vaccines and, secondly, to test drugs that may be used to treat COVID-19 on cells.

For this work, the major pharmaceutical companies required huge volumes of cellswhich they were able to acquire with the aid of an incubator. The newly developed active ingredients were then tested using the cells.

The new vaccines used in the fight against the coronavirus were also repeatedly tested on cells in laboratories and evaluated. An incubator proved to be an essential piece of equipment in a laboratoryparticularly during the coronavirus pandemic.

Read more on premium equipment for virus research.

The Institute of Medical Engineering at the Lucerne University of Applied Sciences and Arts has been carrying out research in the field of space biology. The research team, led by Dr. Fabian Ille, is assisted in its work by a CO2 chamber.

Cells from a bovine hoof are being incubated inside the cabinet at regular intervals until they are needed for a specific experiment. Recently, the cells were frozen and taken to the French city of Bordeaux by Dr. Simon West and a team of researchers.

The reason behind this trip was that the research team in Lucerne was selected by the European Space Agency (ESA) to take part in parabolic flights over the Atlantic. Shortly before the parabolic flights, which lasted for a total of three hours, the cells were removed from the incubator and moved to flight hardware that had been prepared specifically for this purpose and was under controlled temperature conditions.

The scientists from Lucerne wanted to use the parabolic flights to investigate how the cells respond and adapt to mechanical forces. These findings will help them in future attempts to cultivate cartilage that is of a stronger and better consistency, for example. In other words, it might be possible to remove cells from a patient, reproduce them with this innovative new method, and then use them again in the treatment of human patients.

Weightless conditions are helping us to make significant progress, said Dr. Ille, reflecting on the research project so far.

In laboratory tests that have already been carried out, West and Ille have been able to demonstrate in very broad terms that this process could work in the future.In these tests, weightless conditions were simulated using a random position machine. Here again, a CO2 chamber from BINDER was used.

Safety is the absolute top priority here.180C sterilization ensures, for example, that every trial series begins with a clean and fully sterile incubator. Whats more, the fanless design means that germs are not stirred up.

The result is optimal cell growth and absolutely no contamination from airborne germs. A deep-drawn inner chamber without corners or edges also enables the incubator to be cleaned thoroughly with ease. It is therefore no surprise that major pharmaceutical manufacturers choose specifically to put their trust in CO2 incubators from BINDER.

BINDER CO2 incubators are the perfect combination of a range of solutions180C hot air sterilization, rapid control, fixture-free interiors and absolutely zero consumables. For optimal cell growthsafe, reliable, smart, economicallook no further than BINDER.

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If you live with diabetes, you may be aware that having the condition and its complications may put you at greater risk of developing anemia. But how are the two conditions related and what does this mean for you?

This article will investigate the relationship between diabetes and anemia, and what you should know if you have diabetes-related complications impacting your life.

According to the National Heart, Lung, and Blood Institute, Anemia is a condition in which the blood doesnt have enough healthy red blood cells to function properly. This leads to reduced oxygen flow to the bodys organs.

There are more than 3 million cases of anemia diagnosed in the United States every year, making this a very common condition.

You may experience the following symptoms:

Its important to note that some anemia symptoms are similar to symptoms of high blood sugar, including dizziness, lightheadedness, extreme fatigue, rapid heart rate, and headache.

Check your blood sugar often to make sure youre not confusing high blood sugar for suspected anemia. If your symptoms continue for a few days or weeks without high blood sugar numbers or ketones, call a healthcare professional to get checked for anemia.

Diabetes doesnt cause anemia and anemia doesnt cause diabetes. The two conditions are related, though.

Up to 25 percent of Americans with type 2 diabetes also have anemia. So its relatively common for people with diabetes, and especially diabetes-related complications, to also develop anemia.

However, if you have one condition or the other, you wont automatically develop the other condition.

As seen in this 2004 study, Anemia is a common complication of people with diabetes who develop chronic kidney disease because damaged or failing kidneys dont produce a hormone called erythropoietin (EPO), which signals to the bone marrow that the body needs more red blood cells to function.

Early stages of kidney disease (nephropathy) may be asymptomatic, but if youre diagnosed with anemia and you have diabetes, it might be a sign that your kidneys arent working properly.

People with diabetes are also more likely to have inflamed blood vessels. This prevents the bone marrow from even receiving the EPO signal to create more red blood cells to begin with. That makes anemia a more likely result.

Additionally, if you have existing anemia and are then diagnosed with diabetes, it may make you more likely to develop diabetes-related complications, such as retinopathy and neuropathy (eye and nerve damage).

A lack of healthy red blood cells can additionally worsen kidney, heart, and artery health, systems that are already taxed with a life lived with diabetes.

Certain diabetes medications can decrease your levels of the protein hemoglobin, which is needed to carry oxygen through the blood. These diabetes medications can increase your risk of developing anemia:

Since blood loss is also a significant contributor to the development of anemia, if you have diabetes and are on kidney dialysis, you may want to talk with your healthcare team about your increased risk of anemia as well.

Anemia can affect blood sugar levels in several ways.

One 2010 study found that anemia produced false high blood sugar levels on glucose meters, leading to dangerous hypoglycemia events after people overtreat that false high blood sugar.

As shown in a 2014 study, theres a direct link between anemia caused by iron deficiency and higher amounts of glucose in the blood. A 2017 review of several studies found that in people both with and without diabetes, iron-deficiency anemia was correlated with increased A1C numbers.

This resulted from more glucose molecules sticking to fewer red blood cells. After iron-replacement therapy, HbA1c levels in the studies participants decreased.

If you receive an anemia diagnosis and you live with diabetes, there are many excellent treatment options.

Treatment will depend on the underlying cause of the condition, but may include supplementation with iron and/or vitamin B.

If your anemia is caused by blood loss, a blood transfusion may be necessary. If your bodys blood production is reduced, medications to improve blood formation may be prescribed.

Diabetes and anemia are closely related, though neither directly causes the other condition.

Diabetes-related complications such as kidney disease or failure and inflamed blood vessels may contribute to anemia. Certain diabetes medications can also increase the likelihood of developing anemia. Anemia may also make diabetes management more challenging, with higher A1C results, false high blood sugars, and a potential risk of worsening organ health leading to future diabetes complications.

Still, anemia is very treatable with supplementation, dietary or medication changes.

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Newswise CHICAGO (June 10, 2022): Anthony Atala, MD, FACS, Winston-Salem, North Carolina, will be presented with the 2022 Jacobson Innovation Award of the American College of Surgeons (ACS) at a dinner held in his honor this evening in Chicago. He is currently the George Link, Jr. Professor and Director of the Wake Forest Institute for Regenerative Medicine (WFIRM) and the W. H. Boyce Professor and Chair of Urology at the Wake Forest University School of Medicine.

The international surgical award from the ACS honors living surgeons who are innovators of a new development or technique in any field of surgery. It is made possible through a gift from Julius H. Jacobson II, MD, FACS, and his wife Joan. Dr. Jacobson is a general vascular surgeon known for his pioneering work in the development of microsurgery.

Dr. Atala is a pediatric urologist, researcher, professor, and mentor who is renowned for developing foundational principles for regenerative medicine research, which holds great promise for people who require tissue substitution and reconstruction. Dr. Atala and his team successfully implanted the worlds first laboratory grown bladder in 1999.

Dr. Atalas remarkable work has expanded, and today, WFIRM is a leader in translating scientific discovery into regenerative medicine clinical therapies. He currently leads an interdisciplinary team of more than 450 researchers and physicians. Beyond many other world firsts, WFIRM has also developed 15 clinically used technology-based applications, including muscle, urethra, cartilage, reproductive tissues, and skin. Currently, the Institute is working on more than 40 tissues and organs.

Through Dr. Atala's vision, ingenuity, and leadership, the WFIRM team has developed specialized 3-D printers to engineer tissues. This work is accomplished by using cells to create various tissues and organs, including miniature organs called organoids to create body-on-a-chip systems. Dr. Atala and his team also discovered a stem cell population derived from both the amniotic fluid and the placenta, which are currently being used for clinically relevant research applications.

Dr. Atala's theory is that every cell within the human body should be capable of regeneration. What reproduces naturally inside the body should also have the same capabilities of reproduction outside of the body. According to Dr. Atala, the key benefit to the approach of cell and tissue regeneration is that a patient will not reject their own cells or tissue, which is always a concern related to traditional organ match transplantation.

Honors and awards Dr. Atalas innovative work has been recognized as one of Time magazine's Top 10 Medical Breakthroughs in 2007, Smithsonian's 2010 Top Science Story of the Year, and U.S. News & World Report's honor as one of 14 top Pioneers of Medical Progress in the 21st Century. He has been named by Scientific American as one of the world's most influential people in biotechnology, by Life Sciences Intellectual Property Review as one of 50 Key Influencers in the Life Sciences Intellectual Property arena, and by Nature Biotechnology as one of the top 10 Translational Researchers in the World.

Dr. Atala was elected to the Institute of Medicine of the National Academies of Sciences (now the National Academy of Medicine) in 2011 and inducted into the American Institute for Medical and Biological Engineering. In 2014, he was inducted into the National Academy of Inventors as a Charter Fellow and has been a strong and thoughtful contributor to the ACS Surgical Forum and Surgical Research Committee. He presented the prestigious Martin Memorial Named Lecture during the ACS Clinical Congress in 2010 entitled, Regenerative Medicine: New Approaches to Health Care.

Other honors include being the recipient of the U.S. Congress-funded Christopher Columbus Foundation Award, which is bestowed on a living American that currently is working on a discovery that will significantly affect society; the World Technology Award in Health and Medicine for achieving significant and lasting progress; the Edison Science/Medical Award; and the Smithsonian Ingenuity Award.

A national leader in regenerative medicine Throughout his distinguished career, Dr. Atala has led or served on several national professional and government committees, including the National Institutes of Health Working Group on Cells and Developmental Biology, the National Institutes of Health Bioengineering Consortium, and the National Cancer Institute's Advisory Board. He is a founder of the Tissue Engineering Society, the Regenerative Medicine Society, the Regenerative Medicine Foundation, the Alliance for Regenerative Medicine, the Regenerative Medicine Development Organization, the Regenerative Medicine Manufacturing Society, and the Regenerative Medicine Manufacturing Consortium.

A prolific author and inventorDr. Atala is the editor in chief of Stem Cells-Translational Medicine and BioPrinting. He is an author or coauthor of more than 800 journal articles and has applied for or received over 250 national and international patents.

# # #

About Anthony Atala, MD, FACS

Dr. Atala was born in Lima, Peru, and moved to the United States with his family when he was a young boy. He earned a Bachelor of Arts degree from the University of Miami before attending medical school at the University of Louisville, where he also completed his surgical residency training. Near the end of his residency, he applied for a pediatric urology fellowship at Boston Children's Hospital, which was transitioning from a one-year to a two-year program to include a year of research prior to the clinical year. He embarked on a fellowship there in its new form with encouragement from Alan B. Retik, MD, FACS, founder of Boston Childrens first department of urology. Dr. Atala arrived in Boston and began attending seminars, which led him to explore whether uroepithelial cells could be grown and expanded ex vivo, comparable to skin. This additional year of research sparked what has become his career of transformational research, discovery, and innovation with his work focused on growing human cells, tissues, and organs.

Dr. Atala spent the first portion of his academic career at Harvard Medical School before being recruited in 2004 as professor and chair of the department of urology at Wake Forest School of Medicine. After moving his laboratory from Boston, he became the founding Director of the Wake Forest Institute for Regenerative Medicine, where his research and work has produced extraordinary results for nearly two decades.

About the American College of Surgeons The American College of Surgeons is a scientific and educational organization of surgeons that was founded in 1913 to raise the standards of surgical practice and improve the quality of care for all surgical patients. The College is dedicated to the ethical and competent practice of surgery. Its achievements have significantly influenced the course of scientific surgery in America and have established it as an important advocate for all surgical patients. The College has more than 84,000 members and is the largest organization of surgeons in the world. "FACS" designates that a surgeon is a Fellow of the American College of Surgeons.

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Pediatric Urologist Dr. Anthony Atala to Receive 2022 Jacobson Innovation Award of the American College of Surgeons for Pioneering Work in...

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From cities in the sky to robot butlers, futuristic visions fill the history ofPopSci. In theAre we there yet?column we check in on progress towards our most ambitious promises. Read the series and explore all our 150th anniversary coveragehere.

In 1923, Popular Science reported that people were drinking radium-infused water in an attempt to stay young. How far have we come to a real (and non-radioactive) cure for aging?

From the time Marie Curie and her husband Pierre discovered radium in 1898, it was quickly understood that the new element was no ordinary metal. When the Curies finally isolated pure radium from pitchblende (a mineral ore) in 1902, they determined that the substance was a million times more radioactive than uranium. At the time, uranium was already being used in medicine to X-ray bones and even treat cancer tumors, a procedure first attempted in 1899 by Tage Sjogren, a Swedish doctor. Coupled with radiums extraordinary radioactivity and unnatural blue glow, the mineral was soon touted as a cure for everything including cancer, blindness, and baldness, even though radioactivity had only been used to treat malignant tumors. As Popular Science reported in June 1923, it was even believed that a daily glassful of radium-infused water would restore youth and extend life, making it the latest in a long line of miraculous elixirs.

By May 1925 The New York Times was among the first to report cancer cases linked to radium. Two years later, five terminally ill women, who became known as the Radium Girls, sued the United States Radium Corporation where they had worked, hand-painting various objects with the companys poisonous pigment. As more evidence emerged of radiums carcinogenic effects, its cure-all reputation quickly faded, although it would take another half-century before the last of the luminous-paint processing plants was shut down. Radium is still used today in nuclear medicine to treat cancer patients, and in industrial radiography to X-ray building materials for structural defectsbut its baseless status as a life-extending elixir was short-lived.

And yet, radiums downfall did not end the true quest for immortality: Our yearning for eternal youth continues to inspire a staggering range of scientifically dubious products and services.

Since the early days of civilization, when Sumerians etched one of the first accounts of a mortal longing for eternal life in the Epic of Gilgamesh on cuneiform tablets, humans have sought a miracle cure to defy aging and defer death. Five thousand years ago in ancient Egypt, priests practiced corpse preservation so a persons spirit could live on in its mummified host. Fortunately, anti-aging biotech has advanced from mummification and medieval quests for the fountain of youth, philosophers stone, and holy grail, as well as the perverse practices of sipping metal-based elixirs, bathing in the blood of virgins, and even downing Radium-infused water in the early 20th century. But what hasnt changed is that the pursuit of eternal youth has largely been sponsored by humankinds wealthiest citizens, from Chinese emperors to Silicon Valley entrepreneurs.

Weve all long recognized that aging is the greatest risk factor for the overwhelming majority of chronic diseases, whether it be Alzheimers disease, cancer, osteoporosis, cardiovascular diseases, or diabetes, says Nathan LeBrasseur, co-director of The Paul F. Glenn Center for Biology of Aging Research at the Mayo Clinic in Minnesota. But weve really kind of said, well, theres nothing we can do about senescence [cellular aging], so lets move on to more prevalent risk factors that we think we can modify, like blood pressure or high lipids. In the last few decades, however, remarkable breakthroughs in aging research have kindled interest and opened the funding spigots. Fortunately, the latest efforts have been grounded in more established scienceand scientific methodsthan was available in radiums heyday.

In the late 19th century, just as scientists began zeroing in on germs with microscopes, evolutionary biologist August Weismann delivered a lecture on cellular aging, or senescence. The Duration of Life (1881) detailed his theory that cells had replication limits, which explained why the ability to heal diminished with age. It would take 80 years to confirm Weismanns theory. In 1961, biologists Leonard Hayflick and Paul Moorhead observed and documented the finite lifespan of human cells. Another three decades later, in 1993, Cynthia Kenyon, a geneticist and biochemistry professor at the University of California, San Francisco, discovered how a specific genetic mutation in worms could double their lifespans. Kenyons discovery gave new direction and hope to the search for eternal youth, and wealthy tech entrepreneurs were eager to fund the latest quest: figuring out how to halt aging at the cellular level. (Kenyon is now vice president of Calico Research Labs, an Alphabet subsidiary.)

Weve made such remarkable progress in understanding the fundamental biology of aging, says LeBrasseur. Were at a new era in science and medicine, of not just asking the question, what is it about aging that makes us at risk for all these conditions? But also is there something we can do about it? Can we intervene?

In modern aging research labs, like LeBrasseurs, the focus is to tease apart the molecular mechanisms of senescence and develop tools and techniques to identify and measure changes in cells. The ultimate goal is to discover how to halt or reverse the changes at a cellular level.

But the focus on the molecular mechanisms of aging is not new. In his 1940 book, Organisers and Genes, theoretical biologist Conrad Waddington offered a metaphor for a cells life cyclehow it grows from an embryonic state to something specific. In Waddingtons epigenetic landscape, a cell starts out in its unformed state at the top of a mountain with the potential to roll downhill in any direction. After encountering a series of forks, the cell lands in a valley, which represents the tissue it becomes, like a skin cell or a neuron. According to Waddington, epigenetics are the external mechanisms of inheritanceabove and beyond standard genetics, such as chemical or environmental factorsthat lead the cell to roll one way or another when it encounters a fork. Also according to Waddington, who first proposed the theory of epigenetics, once the cell lands in its valley, it will remain there until it diesso, once a skin cell, always a skin cell. Waddington viewed cellular aging as a one-way journey, which turns out to be not so accurate.

We know now that even cells of different types keep changing as they age, says Morgan Levine, who until recently led her own aging lab at the Yale School of Medicine, but is now a founding principal investigator at Altos Labs, a lavishly funded startup. The [Waddington] landscape keeps going. And the new exciting thing is reprogramming, which shows us that you can push the ball back the other way.

Researchers like Levine continue to discover new epigenetic mechanisms that can be used to not only determine a cells age (epigenetic or biological clock) but also challenge Waddingtons premise that a cells life is one way. Cellular reprogramming is an idea first attempted in the 1980s and later advanced by Nobel Prize recipient Shinya Yamanaka, who discovered how to revert mature, specialized cells back to their embryonic, or pluripotent, state, enabling them to start fresh and regrow, for instance, into new tissue like liver cells or teeth.

I like to think of the epigenome as the operating system of a cell, Levine explains. So more or less all the cells in your body have the same DNA or genome. But what makes the skin cell different from a brain cell is the epigenome. It tells a cell which part of the DNA it should use thats specific to it. In sum, all cells start out as embryonic or stem cells, but what determines a cells end state is the epigenome.

Theres been a ton of work done with cells in a dish, Levine adds, including taking skin cells from patients with Alzheimers disease, converting them back to stem cells, and then into neurons. For some cells, you dont always have to go back to the embryonic stem cell, you can just convert directly to a different cell type, Levine says. But she also notes that what works in a dish is vastly different from what works in living specimens. While scientists have experimented with reprogramming cells in vivo in lab animals with limited success, the ramifications are not well understood. The problem is when you push the cells back too far [in their life cycle], they dont know what theyre supposed to be, says Levine. And then they turn into all sorts of nasty things like teratoma tumors. Still, shes hopeful that many of the problems with reprogramming may be sorted out in the next decade. Levine doesnt envision people drinking cellular-reprogramming cocktails to stave off agingat least not in the foreseeable futurebut she does see early-adopter applications for high-risk patients who, lets say, can regrow their organs instead of requiring transplants.

While the quest for immortality is still funded largely by the richest of humans, it has morphed from the pursuit of mythical objects, miraculous elements, and mystical rituals to big business, raising billions to fund exploratory research. Besides Calico and Altos Labs (funded by Russian-born billionaire Yuri Milner and others), theres Life Biosciences, AgeX Therapeutics, Turn Biotechnologies, Unity Biotechnology, BioAge Labs, and many more, all founded in the last decade. While theres considerable hype for these experimental technologies, any actual products and services will have to be approved by regulatory agencies like the Food and Drug Administration, which did not exist when radium was being promoted as a cure-all in the US.

While were working on landing long-term moon shots like editing genomes with CRISPR and reprogramming epigenomes to halt or reverse aging, LeBrasseur sees near-term possibilities in repurposing existing drugs to prop up senescent cells. When a cell gets old and damaged, it has one of three choices: to succumb, in which case it gets flushed from the system; to repair itself because the damage is not so bad; or to stop replicating and hang around as a zombie cell. Not only do [zombie cells] not function properly, explains LeBrasseur, but they secrete a host of very toxic molecules known as senescence associated secretory phenotype, or SASP. Those toxic molecules trigger inflammation, the precursor to many diseases.

It turns out there are drugs, originally targeted at other diseases, that are already in anti-aging trials because theyve shown potential to impact cell biology at a fundamental level, effectively staving off senescence. Although rapamycin was originally designed to suppress the immune system in organ transplant patients, and metformin to assist diabetes patients, both have shown anti-aging promise. When you start looking at data from an epidemiological lens, you recognize that these individuals [like diabetes patients taking metformin] often have less cardiovascular disease, notes LeBrasseur. They also have lower incidence of cancer, and theres some evidence that they may even have lower incidence of Alzheimers disease. Even statins (for cardiovascular disease) and SGL2 inhibitors (another diabetes drug) are being explored for a possible role in anti-aging. Of course, senescence is not all bad. It plays an important role, for example, as a protective mechanism against the development of malignant tumorsso tampering with it could have its downsides. Biology is so smart that weve got to stay humble, right? says LeBrasseur.

Among other things, the Radium Girls taught us to avoid the hype and promise of new and unproven technologies before the pros and cons are well understood. Weve already waited millennia for a miracle elixir, making some horrific choices along the way, including drinking radioactive water as recently as a century ago. The 21st century offers its own share of anti-aging quackery, including unregulated cosmetics, questionable surgical procedures, and unproven dietary supplements. While we may be closer than weve ever been in human history to real solutions for the downsides of aging, there are still significant hurdles to overcome before we can reliably restore youth. It will take years or possibly decades of research, followed by extensive clinical trials, before todays anti-aging research pays dividendsand even then its not likely to come in the form of a cure-all cocktail capable of bestowing immortality. In the meantime, LeBrasseurs advice is simple for those who can afford it: You dont have to wait for a miracle cure. Lifestyle choices like physical activity, nutritional habits, and sleep play a powerful role on our trajectories of aging. You can be very proactive today about how well you age. Unfortunately, not everyone has the means to follow LeBrasseurs medical wisdom. But the wealthiest among usincluding those funding immortalitys questmost definitely do.

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Radium was once cast as an elixir of youth. Are todays ideas any better? - Popular Science

Skin Stem Cells Comments Off on Radium was once cast as an elixir of youth. Are todays ideas any better? – Popular Science | June 11th, 2022

Heart disease is theleading cause of deathamong adults and infants in the U.S. with about 659,000 people dying from heart disease each year, every one in four deaths. Among the many patients with a critical heart condition, about 3,500 are waiting for a heart transplant. Many of them will wait for more than six months, and for some of them time will run out before a transplant becomes available. These alarming statistics illustrate the need for more effective heart tissue replacement strategies.

In contrast to other organs that can repair themselves to various degrees after injury, the heart has limited to no regenerative capacity. When heart cells die during prolonged heart disease or a myocardial infarction, they are replaced by a fibrotic scar that compromises the hearts normal contraction. While modern stem cell technology has enabled production of patient-specific heart cells as a source for tissue engineers, emulating the heart muscles highly structured architecture and complex functionality remains a serious challenge.

The hearts left ventricle pumps blood through our circulatory system by contracting in a torsional wringing motion. This is enabled by layers of cardiomyocytes whose contractile machineries are all aligned in the same direction within an individual layer. Multiple layers are then stacked on top of each other across the 1cm thick heart muscle wall, each oriented at an angle with respect to its neighboring layers. Even though each cardiomyocyte contracts in one direction, the varying alignment of each cardiomyocyte layer causes the ventricle to twist, squeezing the blood within and forcing it to flow to the rest of the body. Tissue engineers have devised different methods to align heart cells on various surfaces but these do not recreate the hearts intricate alignment, nor can they generate myocardial tissue thick enough for use in regenerative heart therapies.

Now, Jennifer Lewis' team at theHarvard John A. Paulson School of Engineering and Applied Sciences(SEAS) and the Wyss Institute for Biologically Inspired Engineering at Harvard University has developed a suite of new heart engineering technologies that has allowed them to mimic the alignment of the hearts contractile elements. Using a bioink with densely packed contractile organ building blocks (OBBs) composed of cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs-CMs), they were able to print aligned cardiac tissue sheets with complex and varied alignment. These sheets have an organization and functionality similar to those in actual human heart muscle layers. The findings are published inAdvanced Materials. In the future, this advance could enable the development of thick multilayered human muscle tissue with more physiological contractile properties.

Being able to effectively mimic the alignment of the hearts contractile system across its entire hierarchy from individual cells to thicker cardiac tissue composed of multiple layers is central to generating functional heart tissue for replacement therapy, said Lewis, senior author of the paper and theHansjrg Wyss Professor of Bioinspired Engineering at SEAS. Lewis is also a Wyss Core Faculty member andco-Lead of the Wyss Institutes 3D Organ Engineering Initiative.

The study builds on Lewis teams 3D bioprinting platform, known assacrificial writing in functional tissue (SWIFT), which allowed them to create cardiac tissue constructs that have the typical high cellular densities of normal heart tissue, usingsophisticated 3D bioprinting capabilities. The approach makes use of preassembled cardiac organ building blocks (OBBs) composed of iPSC-CMs, and allows them to address another grand tissue engineering challenge the introduction of a blood-supporting vascular network using sacrificial inks. However, the resulting tissue constructs did not replicate the complex alignment of the human heart.

To also gain control over directional contractility in engineered layers of heart tissue, we first devised a strategy to program the parallel alignment of iPSC-CMs in developing OBBs, said first-authorJohn Ahrens, who is a graduate student in Lewis group.

To accomplish this, the researchers developed a platform with 1050 individual wells, each containing two micropillars. Into the wells, they seeded hiPSCs-CMs in a mixture with human fibroblast cells and the extracellular matrix (ECM) protein collagen, both of which are essential for heart muscle development. Over time as the cells compact the ECM, they form a dense microtissue in which the cardiomyocytes and their cellular contractile machineries are oriented along the axis connecting the micropillars. The OBBs, called anisotropic OBBs (aOBBs) because they contract in one major direction, are then lifted off the micropillars and used as a feedstock to fabricate a dense bioink. The teams high-throughput approach to the generation of aOBBs also enabled them to fabricate an unprecedented number of contractile building blocks.

The second alignment step is the printing process itself. The mechanical shear forces generated at the print head act on the aOBBs while they are being extruded to give them directionality.

Our lab has previously shown that it was possible to align anisotropic soft materials via 3D printing. Here, we demonstrated that this principle could be applied to cardiac microtissues too, said co-authorSebastien Uzel, who is a Research Associate on Lewis team and mentored Ahrens. To highlight the versatility of their bioprinting process, the researchers printed cardiac tissue sheets with linear, spiral, and chevron geometries in which the contractile aOBBs exhibited significant alignment.

But the team also wanted to be able to measure the contractile features of cardiac constructs printed with aOBBs. For this, they printed long macrofilaments connecting two macropillars, similar to the OBB-generating step using the micropillar platform, only on a larger scale. By measuring the macropillar deflections, they could determine the contractile forces generated by the macrofilaments. The team indeed found that the contractile forces and contraction velocity (speed) increased over a period of seven days which showed that the cardiac filaments kept maturing into actual muscle-like filaments.

With SWIFT, we wanted to address cellular density and tissue scale. Now, by programming alignment, we aimed for mimicking the microarchitecture of the myocardium. One innovation at a time, we are moving closer and closer to engineering functional cardiac tissues for repair or replacement, said Uzel.

For their next order of engineering, the team plans to apply this method to generate more physiological tissues beyond two-dimensional, single layered constructs.

While the holy grail of tissue engineering efforts would be a whole organ heart transplantation, our approach could enable contributions to more immediate applications. It could be used to generate more physiological disease models, and create highly architected myocardial patches that, like LEGO blocks, could match and be used to replace a patient-specific scar after a heart attack, said Ahrens. Similarly, they could be tailored to patch up patient-specific holes in the heart of newborns with congenital heart defects. In theory, these patches could also develop with the child and not have to be replaced as the child grows.

Other authors on the study are present and former members of Lewis team, including Mark Skylar-Scott, who was instrumental in the development of SWIFT, Mariana Mata who assisted with most experiments in this study, as well as Aric Lu and Katharina Kroll. The study was supported by an NSF CELL-MET grant (under grant# EEC-1647837), as well as the Vannevar Bush Faculty Fellowship Program sponsored by the Basic Research Office of the Assistant Secretary of Defense for Research and Engineering through the Office of Naval Research (under grant# N00014-16-1-2823 and N00014-21-1-2958).

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Getting to the heart of engineering a heart - Harvard School of Engineering and Applied Sciences

Cardiac Stem Cells Comments Off on Getting to the heart of engineering a heart – Harvard School of Engineering and Applied Sciences | June 11th, 2022

Stem Cells 101

Every cell type in the body that makes up organs and tissues arose from a more primitive cell type called a stem cell. Stem cells are the foundation of living organisms, with the unique ability to self-renew and differentiate into specialised cell types. There are three different types of stem cell, classified by the number of specialised cell types they can produce: i) pluripotent stem cells (e.g. embryonic stem cells) can generate any specialised cell type; ii) multipotent stem cells (e.g. mesenchymal stem cells) are able to generate multiple, but not all, specialised cell types; and, iii) unipotent stem cells (e.g. epidermal stem cells that produce skin) give rise to only one cell type. It was long believed that stem cell differentiation into specialised cell types only occurs in one direction. There have been many exciting advances in stem cell biology, most notable the discovery of induced pluripotent stem cells (iPSCs) that demonstrated a mature differentiated specialised cell can be reverted to a primitive pluripotent stem cell (Takahashi K, 2006). This discovery transformed our understanding of stem cell biology enabling exciting and substantial advances in stem cell tools, technologies and applications. This article focuses on pluripotent stem cells, as they offer the most promising future applications.

To harness the power of stem cells, they must first be maintained in vitro tissue culture. Culture expansion of stem cells is tricky because they must be maintained in an undifferentiated state and not permitted to differentiate into other cell types until desired. In short, if stem cells are not dividing in log phase growth, they are differentiating. Historically, pluripotent stem cells were notoriously difficult to work with in the lab largely because of the of inherent variability of reagents derived from animal tissues.

An important concept affecting current and future innovations in stem cell technologies is Good Manufacturing Practice (GMP). This is governed by formal regulations administered by drug regulatory agencies (for example the FDA) that control the manufacture processes of medicines. The use of stem cells as therapeutic agents has necessitated specialised drug regulations known as Advanced Therapeutic Medicinal Products (ATMPs). Unlike chemically synthesised medicines where the final product can be defined through chemical analysis, ATMPs are complex biological living entities whereby the entire manufacturing process defines the final product. In simple terms, every reagent that touches the stem cells in the manufacturing process throughout the entire lifetime of the stem cell becomes a component of the final product. As such, in the real world the quality and consistency of the reagents used in a stem cell manufacturing process is paramount for downstream clinical applications, even if the project is still in the R&D or preclinical phase. Once reserved for clinical applications, GMP has become a dominating concept that affects all aspects of stem cell research and applications. Researchers and clinical developers benefit alike from GMP-focused innovations in stem cell technologies that deliver consistent growth properties and high-quality results.

Significant advances that overcome the challenges of the past have been made in all aspects of in vitro stem cell culture. These include advances in tissue culture medium, extracellular matrix, 3D synthetic cell culture plastic, growth factors, dissociation enzymes, cryopreservation agents and differentiation technologies. The workflow to culture stem cells in vitro is not a linear process but rather a continuous circle that can be broken down into 6 steps: 1) Extracellular Matrix coating of tissue culture plasticware; 2) Revival/seeding of tissue culture flasks; 3) Expansion of the cell culture in an incubator; 4) Culture medium change; 5) Subculture or passaging one flask to many; and 6) Cryopreservation of the stem cell culture. The stem cell workflow is shown in Figure 1.

The art of culturing stem cells is a lot easier today than in the past. Stem cells grow as adherent cultures on the surface of tissue culture flasks or dishes (image shown in Figure 1, Step 3). For the stem cells to adhere to the surface it must be coated with extracellular matrix. In the early days, it was an effort to maintain stem cells in culture because the cultures needed to be grown on a feeder layer of fibroblast cells. The requirement for a second cell culture combined with the stem cell culture is laborious to set up and severely limited experiments and applications (due to the contaminating fibroblasts mixed with the stem cells). Extracellular matrix isolated from mouse tumours removed the need for feeder layer cultures but can be variable in consistency and contain contaminants. Today, researchers benefit from recombinantly expressed extracellular matrix containing laminin-511 fragments that provides highly efficient adherence of a broad range of cell types and is easy to use (with only 1 hour coating time required that saves time and cost). Exceptional pluripotent stem cell adherence is achieved with laminin-511 fragments. The recombinant extracellular matrix laminin-511 is expressed in mammalian cell culture (e.g. CHO cells) or insect culture (e.g. silkworm) that eliminates the need for animal derived products in the extracellular matrix. Alternatively, synthetic 3D plastic scaffolds (e.g. Alvetex) are also available that offer a rigid defined matrix that is non-biological.

Early stem cell culture media required the medium to be replenished daily. This means 7 days a week in the lab tending to the stem cell cultures. Optimisation of tissue culture medium composition enables cultures to be maintained over the weekend without a medium change, enabling feeder-free, weekend-free stem cell culture. This may sound insignificant but does have a huge impact on the lifestyle of researchers working with stem cells. Unlike early tissue culture media, the composition of the culture media are fully defined and contain no animal derived products. Removal of animal-derived products offers important advantages by removing variability inherent in animal-derived products and guaranteeing consistent cell growth. Furthermore, animal-free formulations eleminate the risk of infection arising from the animal product (e.g. TSE risk). Growth factors are a critical component of the culture medium to maintain the stem cells in an undifferentiated state. Products available on the market contain growth factors that are expressed and isolated from barley.

Stem cells undergo cellular division in the culture vessel. As they expand, they will eventually outgrow their home and must be subcultured to separate flasks to provide space for further growth. Common practice is to use a digestive enzyme to free the stem cells from the culture surface. Trypsin isolated from bovine is commonplace in the tissue culture laboratory. Advances in the products available today use trypsin expressed in maize that is stable at room temperature in solution. Collagenase is an alternative dissociation reagent that is gentle and efficient on a wide range of cells and is available both animal-free and GMP grade - again enabling robust consistent culture conditions, and removing the dependence on animal derived products that are inherently variable.

The stem cells harvested from cultures can be frozen and stored (or cryopreserved) safely for several decades. When required, the cryopreserved stem cells may be defrosted, revived and expanded in culture providing a renewable source of stem cells. During cryopreservation of stem cells, it is critical to prevent cell death and changes in genotype/phenotype. Todays cryopreservation media can maintain consistent high cell viability after thawing; maintaining cell pluripotency, normal karyotype and proliferation even after long term cell storage. Traditionally, the cryopreservation process involved a rate-controlled freezer or a specialised container to freeze the cells at -1C/min. Advances in cryopreservation agents have removed the need for rate-controlled freezing. The process is now simple - you just place the stem cell suspension into a -80C freezer. Moreover, cryopreservation agents are available in GMP grade and with no animal-derived ingredients.

The power of stem cells lies in their ability both to self-renew and to differentiate into specialised cell types. The process of differentiation removes the stem cells from the workflow towards applications. Directed differentiation of stem cells into specific cell types enables the number of applications to grow. A typical differentiation protocol uses stepwise changes in culture medium, cytokines, growth factors and extracellular matrix over several weeks to direct the stem cells into a particular lineage and fate. Today, innovative technologies use genetic reprogramming factors that rapidly (< 1 week) differentiate stem cells into mature cell phenotypes. This advance significantly reduces time to experiment and increases manufacturing capacity for differentiated cell types.

Table 1. Advances in Stem Cell Technologies.Description Area of Innovation Examples of Innovative ProductsExtracellular Matrix Recombinant Laminin Expressed in CHO and Silkworm iMatrix-511Culture Medium No medium change required over the weekend, GMP grade, animal free StemFit MediumGrowth Factors Recombinant, GMP grade, animal free StemFit PuroteinDissociation Reagents Trypsin enzyme recombinantly expressed in maize. Collagenase & Neutral Protease expressed in Clostridium histolyticum TrypLECollagenase NBNeutral Protease NBCryopreservation Rate-controlled freezing not required. GMP grade, animal free and available for clinical use. Suitable for all cell types. STEM-CELLBANKERDifferentiation Rapid directed differentiation through genetic reprogramming Quick-Skeletal MuscleQuick-EndotheliumQuick-Neuron

There are unlimited applications that arise from a renewable source of mature cell types. One exciting area of innovation using differentiated stem cells is in disease modelling. Studying a disease state in an organ or tissue has in the past been limited to using in vivo animal models; whereas, differentiated stem cells opened the opportunity to create disease states in specific cell types in vitro. In addition, current technologies enable organoids or mini organs to be generated in the laboratory. Disease specific induced pluripotent stem cells can also be used to create disease models in vitro that are valuable tools for the study of disease and drug development without the need for in vivo animal models. In theory, any tissue is possible to create in vitro. In an exciting example of stem cell disease modelling, Dr Takayama from the CiRA in Kyoto, Japan has successfully modelled the life cycle of SARS-CoV-2 in both organoids and undifferentiated pluripotent stem cells (Takayama, 2020) (Sano, 2021) (Figure 2). In another example, the Skeletal Muscle Differentiation Kit was used to produce skeletal muscle myotubes from stem cells to create an in vitro disease model (Figure 3). In a direct application, pluripotent stem cell models of skeletal muscle have also been successfully used to develop a novel treatment for Duchenne muscular dystrophy (Moretti, 2020).

Promising progress is being made to create meat in the laboratory or what is commonly called cultured meat. Environmental concerns are driving the need for more sustainable meat production over traditional farming methods. Stem cell research in itself is reducing the need for the use of animals across multiple aspects as highlighted here. Producing cultured meat is straightforward in principle but faces many challenges in practice, for example maintaining the correct environment and stimuli for cultured cells to produce meat with the correct consistency and characteristics of the animal derived product. Stem cell cultures are expanded at scale in bioreactors and differentiated into skeletal muscle cells. These can be structured, using an edible scaffold for example, or used unstructured as the raw material to produce meat products (Figure 4). Tools and technologies are readily available to achieve this goal: expansion and differentiation of stem cells is highly efficient. However, a key consideration is the cost of goods. Current technologies are too costly but these are pioneering times and research is moving at an exciting pace.

The promise and potential of stem technologies to advance biology, medicine and food production can only be fulfilled if stem cell culture conditions are consistent, and accessible to research scientists and commercial operations alike. Exciting advances across multiple aspects of the stem cell workflow have streamlined processes to deliver products that are fully defined and animal-free. Furthermore, clinical translation of stem cell therapies and drug discovery are accelerated by the availability of GMP compliant reagents. The foundations are set for a bright future of discoveries and applications emerging from stem cell technologies.

Dr William Hadlington-Booth is the business unit manager for stem cell technologies and the extracellular matrix at AMSBIO. Erik Miljan, PhD, is a pioneer in the development of cellular therapies for a range of degenerative and disease conditions. He holds a PhD in biochemistry from Hong Kong University. For further information please contact:William@amsbio.com

Moretti, A. F., et al. (2020). Somatic gene editing ameliorates skeletal and cardiac muscle failure in pig and human models of Duchenne muscular dystrophy. Nature Medicine, 26, 207214.Takahashi K., et al. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. . Cell, 126, 663-676.Takayama, K. (2020). In Vitro and Animal Models for SARS-CoV-2 research. Trends in Pharmacological Sciences, 41. 513-517.Sano, E., et al. (2021). Modeling SARS-CoV-2 infection and its individual differences with ACE2-expressing human iPS cells. Iscience, 24(5), 102428.

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Current and Future Innovations in Stem Cell Technologies - Labmate Online

Cardiac Stem Cells Comments Off on Current and Future Innovations in Stem Cell Technologies – Labmate Online | June 11th, 2022

"It actually changed my life," said Taylor, who directed regenerative medicine research at Texas Heart Institute in Houston until 2020. "I said to myself, 'Oh my gosh, that's life.' I wanted to figure out the how and why, and re-create that to save lives."

That goal has become reality. On Wednesday at the Life Itself conference, a health and wellness event presented in partnership with CNN, Taylor showed the audience the scaffolding of a pig's heart infused with human stem cells -- creating a viable, beating human heart the body will not reject. Why? Because it's made from that person's own tissues.

"Now we can truly imagine building a personalized human heart, taking heart transplants from an emergency procedure where you're so sick, to a planned procedure," Taylor told the audience.

"That reduces your risk by eliminating the need for (antirejection) drugs, by using your own cells to build that heart it reduces the cost ... and you aren't in the hospital as often so it improves your quality of life," she said.

Debuting on stage with her was BAB, a robot Taylor painstakingly taught to inject stem cells into the chambers of ghost hearts inside a sterile environment. As the audience at Life Itself watched BAB functioning in a sterile environment, Taylor showed videos of the pearly white mass called a "ghost heart" begin to pinken.

"It's the first shot at truly curing the number one killer of men, women and children worldwide -- heart disease. And then I want to make it available to everyone," said Taylor to audience applause.

"She never gave up," said Michael Golway, lead inventor of BAB and president and CEO of Advanced Solutions, which designs and creates platforms for building human tissues.

"At any point, Dr. Taylor could have easily said 'I'm done, this just isn't going to work. But she persisted for years, fighting setbacks to find the right type of cells in the right quantities and right conditions to enable those cells to be happy and grow."

Giving birth to a heart

"We were putting cells into damaged or scarred regions of the heart and hoping that would overcome the existing damage," she told CNN. "I started thinking: What if we could get rid of that bad environment and rebuild the house?"

Soon, she graduated to using pig's hearts, due to their anatomical similarity to human hearts.

"We took a pig's heart, and we washed out all the cells with a gentle baby shampoo," she said. "What was left was an extracellular matrix, a transparent framework we called the 'ghost heart.'

"Then we infused blood vessel cells and let them grow on the matrix for a couple of weeks," Taylor said. "That built a way to feed the cells we were going to add because we'd reestablished the blood vessels to the heart."

The next step was to begin injecting the immature stem cells into the different regions of the scaffold, "and then we had to teach the cells how to grow up."

"We must electrically stimulate them, like a pacemaker, but very gently at first, until they get stronger and stronger. First, cells in one spot will twitch, then cells in another spot twitch, but they aren't together," Taylor said. "Over time they start connecting to each other in the matrix and by about a month, they start beating together as a heart. And let me tell you, it's a 'wow' moment!"

But that's not the end of the "mothering" Taylor and her team had to do. Now she must nurture the emerging heart by giving it a blood pressure and teaching it to pump.

"We fill the heart chambers with artificial blood and let the heart cells squeeze against it. But we must help them with electrical pumps, or they will die," she explained.

The cells are also fed oxygen from artificial lungs. In the early days all of these steps had to be monitored and coordinated by hand 24 hours a day, 7 days a week, Taylor said.

"The heart has to eat every day, and until we built the pieces that made it possible to electronically monitor the hearts someone had to do it person -- and it didn't matter if it was Christmas or New Year's Day or your birthday," she said. "It's taken extraordinary groups of people who have worked with me over the years to make this happen."

But once Taylor and her team saw the results of their parenting, any sacrifices they made became insignificant, "because then the beauty happens, the magic," she said.

"We've injected the same type of cells everywhere in the heart, so they all started off alike," Taylor said. "But now when we look in the left ventricle, we find left ventricle heart cells. If we look in the atrium, they look like atrial heart cells, and if we look in the right ventricle, they are right ventricle heart cells," she said.

"So over time they've developed based on where they find themselves and grown up to work together and become a heart. Nature is amazing, isn't she?"

Billions and billions of stem cells

As her creation came to life, Taylor began to dream about a day when her prototypical hearts could be mass produced for the thousands of people on transplant lists, many of whom die while waiting. But how do you scale a heart?

"I realized that for every gram of heart tissue we built, we needed a billion heart cells," Taylor said. "That meant for an adult-sized human heart we would need up to 400 billion individual cells. Now, most labs work with a million or so cells, and heart cells don't divide, which left us with the dilemma: Where will these cells come from?"

"Now for the first time we could take blood, bone marrow or skin from a person and grow cells from that individual that could turn into heart cells," Taylor said. "But the scale was still huge: We needed tens of billions of cells. It took us another 10 years to develop the techniques to do that."

The solution? A bee-like honeycomb of fiber, with thousands of microscopic holes where the cells could attach and be nourished.

"The fiber soaks up the nutrients just like a coffee filter, the cells have access to food all around them and that lets them grow in much larger numbers. We can go from about 50 million cells to a billion cells in a week," Taylor said. "But we need 40 billion or 50 billion or 100 billion, so part of our science over the last few years has been scaling up the number of cells we can grow."

Another issue: Each heart needed a pristine environment free of contaminants for each step of the process. Every time an intervention had to be done, she and her team ran the risk of opening the heart up to infection -- and death.

"Do you know how long it takes to inject 350 billion cells by hand?" Taylor asked the Life Itself audience. "What if you touch something? You just contaminated the whole heart."

Once her lab suffered an electrical malfunction and all of the hearts died. Taylor and her team were nearly inconsolable.

"When something happens to one of these hearts, it's devastating to all of us," Taylor said. "And this is going to sound weird coming from a scientist, but I had to learn to bolster my own heart emotionally, mentally, spiritually and physically to get through this process."

Enter BAB, short for BioAssemblyBot, and an "uber-sterile" cradle created by Advance Solutions that could hold the heart and transport it between each step of the process while preserving a germ-free environment. Taylor has now taught BAB the specific process of injecting the cells she has painstakingly developed over the last decade.

"When Dr. Taylor is injecting cells, it has taken her years to figure out where to inject, how much pressure to put on the syringe, and the best speed and pace to add the cells," said BAB's creator Golway.

"A robot can do that quickly and precisely. And as we know, no two hearts are the same, so BAB can use ultrasound to see inside the vascular pathway of that specific heart, where Dr. Taylor is working blind, so to speak," Golway added. "It's exhilarating to watch -- there are times where the hair on the back of my neck literally stands up."

Taylor left academia in 2020 and is currently working with private investors to bring her creation to the masses. If transplants into humans in upcoming clinical trials are successful, Taylor's personalized hybrid hearts could be used to save thousands of lives around the world.

In the US alone, some 3,500 people were on the heart transplant waiting list in 2021.

"That's not counting the people who never make it on the list, due to their age or heath," Taylor said. "If you're a small woman, if you're an underrepresented minority, if you're a child, the chances of getting an organ that matches your body are low.

If you do get a heart, many people get sick or otherwise lose their new heart within a decade. We can reduce cost, we can increase access, and we can decrease side effects. It's a win-win-win."

Taylor can even envision a day when people bank their own stem cells at a young age, taking them out of storage when needed to grow a heart -- and one day even a lung, liver or kidney.

"Say they have heart disease in their family," she said. "We can plan ahead: Grow their cells to the numbers we need and freeze them, then when they are diagnosed with heart failure pull a scaffold off the shelf and build the heart within two months.

"I'm just humbled and privileged to do this work, and proud of where we are," she added. "The technology is ready. I hope everyone is going to be along with us for the ride because this is game-changing."

Original post:
'Ghost heart': Built from the scaffolding of a pig and the patient's cells, this cardiac breakthrough may soon be ready for transplant into humans -...

Cardiac Stem Cells Comments Off on ‘Ghost heart’: Built from the scaffolding of a pig and the patient’s cells, this cardiac breakthrough may soon be ready for transplant into humans -… | June 11th, 2022

Owing to Rising Demand for Less Invasive Treatments Among Heart Patients, Fact.MR Study Opines the Global Bioabsorbable Stents Market Share is Estimated to Reach a Value of Nearly US$ 1 Billion by 2032 from US$ 372 Million in 2021

Growing incidences of physicians and healthcare professionals preferring bioabsorbable stents over conventional stents is believed to have rapidly surged the bioabsorbable stent market growth in the global market.

Fact.MR, a Market Research and Competitive Intelligence Provider - The global bioabsorbable stents market is predicted to witness a moderate growth rate of 9.6% during the forecast years 2022 to 2032. The net worth of the bioabsorbable stents market share is expected to be valued at around US$ 1 Billion by the year 2032, growing from a mere US$ 372 Million recorded in the year 2021.

The growing prevalence of cardiovascular disease is sighted to be the leading cause of heart-related mortality worldwide. Around 17.5 million people die each year as a result of cardiovascular disease as a consequence of changing lifestyles, dietary habits, and rising blood pressure difficulties. All these factors have boosted the demand for bioabsorbable stents in the global market.

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Cardiovascular illnesses were responsible for more than 32% of fatalities in 2015, and this number is anticipated to grow to 45 per cent by 2030. The number of people diagnosed with diabetes has increased. Obesity, which is the leading cause of type 2 diabetes in adults, has increased as a result of changes in trends, food patterns, and regular exercise. The proliferation of such correlated diseases is suggested to be the major driving factor for the sales of bioabsorbable stents across the globe.

However, due to an increase in the prevalence of coronary artery disease, increased knowledge of bioabsorbable stents, increased demand for minimally invasive surgery, and increased adoption of unhealthy lifestyles, Asia-Pacific is predicted to have the highest CAGR from 2021 to 2032.

What is the Bioabsorbabale Stents Market Outlook in Asia Pacific Region?

As per the global market study on bioabsorbable stents, Asia Pacific is predicted to develop at the quickest rate. The rising number of cardiac patients in the Asia Pacific countries with the highest population count is predicted to drive the demand for bioabsorbable stents in the regional market.

During the projected period, the China bioabsorbable stents market is predicted to lead at the fastest rate of 8.8% in this geographical region. The net worth of the market is estimated to be around US$ 28 Million in 2022 and is projected to reach a total valuation of US$ 71.6 Million in the year 2032.

Other than that, bioabsorbable stents market opportunities in Japan and South Korea are also quite promising for the forecasted years, with an estimated growth rate of 8.1% and 7.3%, respectively. This new market research report on bioabsorbable stents also sheds light on the growth prospects in Indian Market as well.

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Key Takeaways from Market Study

Competitive Landscape

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Recent Developments in the Market

Fact.MRs Domain Expertise in Healthcare Sector

Our healthcare consulting team guides organizations at each step of their business strategy by helping you understand how the latest influencers account for operational and strategic transformation in the healthcare sector. Our expertise in recognizing the challenges and trends impacting the global healthcare industry provides indispensable insights and support - encasing a strategic perspective that helps you identify critical issues and devise appropriate solutions.

Point of Care Diagnostics Market - Shipments of point of care test (POCT) kits are projected to surge at a CAGR of around 7% from 2021 to 2028, as per this new analysis. In 2020, the global point of care diagnostics market stood at US$ 34.1 Bn, and is anticipated to surge to a valuation of US$ 66 Bn by the end of 2028.

Spectrometry Market - The global spectrometry market is projected to increase from a valuation of US$ 7.1 Bn in 2020 to US$ 13.8 Bn by 2028, expanding at a CAGR of 6.4% during the forecast period, Demand for mass spectrometry is set to increase faster at a CAGR of 7.4% over the forecast period 2021-2028.

Coronary Stents Market- Worldwide sales of coronary stents were valued at around US$ 10.1 Bn in 2020. The global coronary stents market is projected to register 12.9% CAGR and reach a valuation of US$ 25.7 Bn by the end of 2028.

Osteoporosis Therapeutics Market- The global osteoporosis therapeutics market stands at a valuation of US$ 12.7 Bn currently, and is predicted to reach US$ 14.2 Bn by the end of 2026. Consumption of osteoporosis therapeutic drugs is anticipated to increase at a CAGR of 2.9% from 2022 to 2026.

CNS Therapeutics Market- The CNS therapeutics market stands at a valuation of US$ 116.7 Bn in 2022, and is expected to reach US$ 142.1 Bn by the end of 2026. CNS drug sales are projected to rise at a steady CAGR of 4.9% from 2022 to 2026.

Induced Pluripotent Stem Cell (iPSC) Market- The global induced pluripotent stem cell (iPSC) market stands at a valuation of US$ 1.8 Bn in 2022, and is projected to climb to US$ 2.3 Bn by the end of 2026. Over the 2022 to 2026 period, worldwide demand for induced pluripotent stem cells is anticipated to rise rapidly at a CAGR of 6.6%.

Doxorubicin Market- Demand for doxorubicin is anticipated to increase steadily at a CAGR of 5.3% from 2022 to 2026. At present, the global doxorubicin market stands at US$ 1.1 Billion, and are projected to reach a valuation of US$ 1.3 Billion by the end of 2026.

Heart Attack Diagnostics Market- The heart attack diagnostics market is predicted to grow at a moderate CAGR of 7.1% during the forecast period of 2022 to 2032. The global heart attack diagnostics market is estimated to reach a value of nearly US$ 22.2 Billion by 2032 by growing from US$ 10.4 Billion in 2021.

Smart Implants Market- The global smart implants market is estimated at US$ 3.9 billion in 2022, and is forecast to surpass a market value of US$ 22.2 billion by 2032. Smart implants are expected to contribute significantly to the global implants market, with demand surging at a CAGR of 19% from 2022 to 2032.

Facial Implants Market- The global facial implant market was valued at US$ 2.7 Billion in 2022, and is expected to rise at a 7.7% value CAGR, likely to reach US$ 5.6 Billion by the end of the 2022-2032 forecast period.

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Continued here:
Bioabsorbable Stents Market to Grow at a Fine CAGR of 9.6% through 2032: Improvements in Healthcare Infrastructure and Growing Geriatric Population to...

Cardiac Stem Cells Comments Off on Bioabsorbable Stents Market to Grow at a Fine CAGR of 9.6% through 2032: Improvements in Healthcare Infrastructure and Growing Geriatric Population to… | June 11th, 2022

Abstract: Electrical stimulation influences neural stem cell neurogenesis. We analyzed the effects of electrical stimulation on neurogenesis in rodent spinal cord-derived neural stem cells (SC-NSCs) in vitro and in vivo and evaluated functional recovery and neural circuitry improvements with electrical stimulation using a rodent spinal cord injury (SCI) model. Rats (20 rats/group) were assigned to a sham (Group 1), SCI only (Group 2), SCI + electrode implant without stimulation (Group 3), and SCI + electrode with stimulation (Group 4) groups to count total SC-NSCs and differentiated neurons and evaluate morphological changes in differentiated neurons. Further, the Basso, Beattie, and Bresnahan scores were analyzed, and the motor and somatosensory evoked potentials in all rats were monitored. In vitro, biphasic electrical currents increased SC-NSC proliferation and neuronal differentiation and caused qualitative morphological changes in differentiated neurons. Electrical stimulation promoted SC-NSC proliferation and neuronal differentiation and improved functional outcomes and neural circuitry in SCI models. Increased Wnt3, Wnt7, and -catenin protein levels were also observed after electrical stimulation. In conclusion, our study proved the beneficial effects of electrical stimulation on SCI. We believe that Wnt/-catenin pathway activation may be associated with this relationship between electrical stimulation and neuronal regeneration after SCI.

The rest is here:
Effect of Electrical Stimulation on Spinal Cord Injury: In Vitro and In Vivo Analysis - Newswise

Spinal Cord Stem Cells Comments Off on Effect of Electrical Stimulation on Spinal Cord Injury: In Vitro and In Vivo Analysis – Newswise | June 11th, 2022

A 12-year-old boy's parents in the United Kingdom are trying to keep him hooked up to life support systems after doctors have said they believe he is "brain stem dead."

Archie Battersbee's mother and father, Holly Dance and Paul Battersbee want to give their son every chance at life after he was found unconscious on April 7 with a ligature around his neck. He reportedly had participated in what is believed to be an online blackout challenge, according to watchdog Christian Concern.

The boy is in critical condition at the Royal London Hospital.

His parents say a video of Archie gripping his mother's fingers is proof that he's still alive and his brain is functioning.

But his doctors believe there's no hope for the boy to recover since they believe his brain stem is dead. Scans show blood is not flowing to the area, according to Sky News. The stem lies at the base of the brain above the spinal cord. It is responsible for regulating most of the body's automatic functions essential for life. Doctors have said Archie's stem is 50% damaged and that 10% to 20% of the stem is in necrosis - where cells have died and/or are decaying.

Lawyers for the Barts Health NHS Trust said that doctors have repeatedly recreated the moment of the boy holding a clinician's hand, but the hospital workers felt "friction" not a grip, which the doctors say is consistent with muscle stiffness.

The hospital group has asked the Family Division of the High Court to rule that it is in Archie's 'best interests' to die by removing life support. However, Archie's family is not convinced that he is brain dead. They have experienced behavior that contradicts what the hospital first told them, and have also seen stories of remarkable recoveries from similar conditions in other patients, according to Christian Concern.

A High Court judge will decide if the boy will be taken off life support.

On Thursday, Archie's mother sat down for an interview with Christian Concern. She said she's fighting to keep her son alive.

Archie's mother Holly also told Sky News her son has not been given enough time to recover from his brain injury. "I don't understand the rush," she said. "I know they haven't got a lot of beds in hospital, but I don't understand the rush."

"I know he's in there and I know all that child needs is time. My gut instinct is spot on. My child is in there. He needs time to heal," she said.

An online petition to the hospital's chief executive officer has been created to ask that legal action be withdrawn in Archie's case. So far, almost 68,000 people have signed it.

Watch Christian Concern's video about Archie Battersbee below:

***Please sign up forCBN Newslettersand download theCBN News appto ensure you keep receiving the latest news from a distinctly Christian perspective.***

Read more:
UK Judge to Decide if 12-Year-Old Will Be Removed from Life Support, Parents Beg for More Time to Heal - CBN.com

Spinal Cord Stem Cells Comments Off on UK Judge to Decide if 12-Year-Old Will Be Removed from Life Support, Parents Beg for More Time to Heal – CBN.com | June 11th, 2022

Newswise LOS ANGELES (June 9, 2022) --Investigators from Cedars-Sinai will present the latest novel stem cell and regenerative medicine research at the International Society for Stem Cell Research (ISSCR) Annual Meeting, which is being held in person and virtually June 15-19 in San Francisco.

At this years scientific forum,Clive Svendsen, PhD, a renowned scientist and executive director of theCedars-SinaiBoard of Governors Regenerative Medicine Institute, willassume the role as treasurerfor the organization. In this position, he will be working with leading scientists, clinicians, business leaders, ethicists, and educators to pursue the common goal of advancing stem cell research and its translation to the clinic.

Along with taking on this leadership role, Svendsens work on a combination stem cell-gene therapy for the treatment of amyotrophic lateral sclerosis, afatal neurological disorder known as ALS or Lou Gehrig's disease, was selected as a Breakthrough Clinical Advances abstract and one ofthe years most compelling pieces of stem cell science. Svendsen will present data from the first spinal cord trial and a synopsis of the ongoing cortical trial and the potential impact this may have on this devastating disease.

The breakthrough oral session, A new trial transplanting neural progenitors modified to release GDNF into the motor cortex of patients with ALS, takes place on Thursday, June 16, from 5:15 to 7 p.m. The presentation is part of the Biotech, Pharma and AcademiaBringing Stem Cells to Patients Clinical Applications track.

Through this highly collaborative work, we hope to develop new therapeutic options for patients with such a debilitating and deadly disease, said Svendsen, who is also the Kerry and Simone Vickar Family Foundation Distinguished Chair in Regenerative Medicine.

All abstracts are embargoed until the start of each individual presentation.

Additional noteworthy presentations featuring Cedars-Sinai investigators at ISSCR 2022 include:

FollowCedars-Sinai Academic Medicineon Twitterfor more on the latest basic science and clinical research from Cedars-Sinai.

See original here:
First-of-its-Kind Stem Cell and Gene Therapy Highlighted at Annual Stem Cell Meeting - Newswise

Spinal Cord Stem Cells Comments Off on First-of-its-Kind Stem Cell and Gene Therapy Highlighted at Annual Stem Cell Meeting – Newswise | June 11th, 2022

More than 500 million people have been diagnosed with COVID-19 since late 2019. Most people who develop COVID-19 have mild disease, but theres compelling evidence that people with certain health conditions like leukemia are at elevated risk of severe disease or death.

A 2021 study presented at the 63rd American Society of Hematology Annual Meeting and Exposition found that people with blood cancer have a 17 percent chance of dying from COVID-19, significantly higher than the general population.

Its less clear if COVID-19 increases your risk of developing leukemia or other blood cancers. Some researchers think its plausible that COVID-19, in combination with other factors, could contribute to cancer development. At this time, the link remains theoretical.

Read on to learn more about how COVID-19 could, in theory, contribute to the development of leukemia.

Some types of blood cancer have been linked to infections. Its not clear if COVID-19 contributes to the development of leukemia, but scientists have found some theoretical links.

Cancer development is usually a consequence of multiple factors that drive genetic mutations in cancer cells. Its plausible that COVID-19 could predispose your body to cancer or accelerate cancer progression.

Most people with COVID-19 recover within 2 to 6 weeks, but some people have symptoms that linger for months. Its thought that the lingering effects result from chronic low grade inflammation triggered by the SARS-CoV-2 virus that causes COVID-19.

Chronic inflammation can cause DNA damage that contributes to the development of cancer. In a study published in April 2021, researchers hypothesized lingering inflammation in people with COVID-19 could increase cancer risk.

The immune response in people with COVID-19 is orchestrated by pro-inflammatory molecules linked to the development of tumors, specifically:

COVID-19 is also associated with other processes known to drive cancer formation such as:

A few case studies have reported people admitted to the hospital with leukemia shortly after developing COVID-19. However, its not clear if COVID-19 played a role or how much of a role it played. Leukemia may have developed coincidentally.

The authors of a 2022 study present a theoretical framework of how COVID-19 could influence the development of blood cancers. According to the researchers, an abnormal immune response to viral infections can indirectly trigger gene mutations that promote leukemia.

The virus that causes COVID-19 can also significantly interact with the renin-angiotensin system, which is suggested to have a role in the development of cancerous blood cells.

In a case study published in 2021, researchers present the case of a 61-year-old man who developed acute myeloid leukemia 40 days after developing COVID-19. The researchers concluded that more studies are needed to assess whether theres an association between COVID-19 and acute leukemia.

In another case study from 2020, researchers presented a man who developed COVID-19 as the first sign of chronic lymphocytic leukemia (CLL). The researchers found that the persons lymphocyte count doubled over 4 weeks, suggesting the viral infection is associated with the replication of B cells, the type of white blood cell that CLL develops in.

Some other types of viral infections have been linked to the development of leukemia.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and its rates have been increasing. Growing evidence strongly suggests an abnormal immune response to infections early in life is responsible.

Having a human adult T-cell leukemia virus type 1 infection is linked to the development of T-cell leukemia. This virus is transmitted primarily through bodily fluids. The World Health Organization estimates that 5 to 10 million people have the viral infection.

Some types of infections have been linked to the development of another type of blood cancer called lymphoma. They include:

The FDA has approved the drug remdesivir for adults and some children with COVID-19.

At the time of writing, theres no evidence that remdesivir can cause leukemia.

In a 2021 study, a 6-year-old child with newly diagnosed ALL and COVID-19 was treated with remdesivir and convalescent plasma therapy before starting leukemia treatment.

No adverse events were linked to the therapy, and the researchers concluded this treatment could be considered in people with cancer to accelerate the resolution of the viral infection and to start cancer treatment sooner.

Some researchers have raised concerns that the antiviral drug molnupiravir, which received FDA Emergency Use Authorization on December 23, 2021, could potentially cause cancerous mutations or birth defects. Researchers are continuing to examine these potential adverse effects.

The development of blood cancer is complex. Researchers are continuing to examine whether COVID-19 infection can contribute to the development of leukemia or any other blood cancer. Some researchers have posed a theoretical link, but more research is needed.

None of the vaccines approved for use in the United States interact with your DNA or cause cancer, according to the Centers for Disease Control and Prevention (CDC). Its a myth that mRNA vaccines (Pfizer-BioNTech and Moderna) can cause changes to your DNA.

About 25 percent of blood cancer patients dont produce detectable antibodies after vaccination, according to the Leukemia & Lymphoma Society (LLS). However, the CDC continues to recommend that everyone with cancer still get vaccinated.

LLS experts say vaccination should be combined with other prevention precautions for the best protection.

People with cancer seem to be at a higher risk of severe COVID-19. According to the National Cancer Institute, people with blood cancer may have a higher risk of prolonged infection and death than people with solid tumors.

Researchers are continuing to examine the link between leukemia and COVID-19. Strong evidence suggests that people with leukemia are at an increased risk of developing severe COVID-19.

Some researchers have posed that COVID-19 could contribute to leukemia formation, but as of now, the link remains theoretical. Much more research is needed to understand the connection.

Excerpt from:
Leukemia After COVID-19: Is There a Connection? - Healthline

Bone Marrow Stem Cells Comments Off on Leukemia After COVID-19: Is There a Connection? – Healthline | May 29th, 2022

The success story of two young children who were the first to receive paediatric bone morrow transplants in the UAE was shared at an event in Abu Dhabi.

Burjeel Medical Citys bone marrow transplant unit, which was inaugurated in the capital in September, carried out the procedures on Jordana, 5, and Ahmed Daoud Al Uqabi, 2, just two weeks apart in April.

Both are now on the road to recovery and act as examples of the life-saving work being performed under a landmark health strategy.

Previously patients in the Emirates requiring bone marrow transplants would have to seek medical treatment abroad.

In the next two years, doctors hope to cut by half the number of patients needing to undergo such transplant procedures.

They spoke of efforts to drive forward the country's health sector at the first Emirates Paediatric Bone Marrow Transplant Congress in Abu Dhabi on Friday.

Jordana's donor for the milestone procedure was her 10-year-old sister Jolina. Photo: Burjeel Medical City

Two-year-old Ahmed Daoud Al Uqabi was the first child with thalassemia, a genetic defect in the composition of haemoglobin, to receive a bone marrow transplant at the Burjeel unit. His donor was an older sibling.

He had travelled to the Emirates from Iraq for treatment, highlighting the UAE's mission to deliver world-class health care and become a centre for medical tourism.

Jordana, 5, from Uganda, who has sickle-cell anaemia, benefited from a matched sibling transplant that involved her receiving healthy stem cells from her sister Jolina, 10.

Her sister attended the Abu Dhabi conference, along with their mother.

The allogeneic stem cell transplant involves transferring healthy blood stem cells from a donor to replace a patients diseased or damaged bone marrow.

The complex procedure requires collecting stem cells from the donor's blood, bone marrow within a donor's hipbone, or from the blood of a donated umbilical cord, before transferring them to the patient.

Dr Zainul Aabideen, head of paediatric haematology and oncology at BMC, said after Jordana's surgery that she had endured great pain and suffering in her life.

Two-year-old Ahmed Daoud Al Uqabi was the first child with thalassemia, a genetic defect in the composition of haemoglobin, to receive a bone marrow transplant at the Burjeel unit. Photo: VPS Healthcare

The only curative option for this life-threatening condition is bone marrow transplantation," Dr Aabideen said.

"Prior to this procedure, there would have been immense suffering for the patient. The entire care team here at the hospital, as well as the childs parents, are delighted that the transplant will remove this pain from her life.

Both Ahmed and Jordana are on the road to recovery and medics have their sights set on helping hundreds more like them.

"Abu Dhabi is currently distinguished by the application of the highest standards used in the treatment of bone marrow transplantation," said Dr Fatima Al Kaabi, director of the Abu Dhabi Bone Marrow Transplant Programme at the Abu Dhabi Stem Cell Centre.

"Providing these distinguished services in the country makes it easier for us as specialists in this field to provide medical care ... in addition to reducing costs compared with treatment abroad.

"We expect, during the next two years, with the presence of bone marrow transplants for children, to reduce requests for treatment abroad for these cases to 50 per cent.

Updated: May 28, 2022, 3:45 AM

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First children in UAE to receive bone marrow transplants bring hope to others - The National

Bone Marrow Stem Cells Comments Off on First children in UAE to receive bone marrow transplants bring hope to others – The National | May 29th, 2022

DirectCell system (Biogennix)

Biogennix has announced that itsDirectCelladvanced bone grafting systemhas now been used in more than 500 cases.

The DirectCell system includes a bone graft product with advanced bone regeneration properties along with novel instrumentation engineered to harvest high concentrations of patient stem cells, say Biogennix.

The cell-stimulating graft within the system is theadvanced synthetic bone graft, Agilon, which is available in a mouldable and strip form. Agilon products are based on Biogennixs TrelCor technologythat contains ananocrystalline hydroxycarbanoapatite graft surfacewhich actively participates in bone regeneration.

The DirectCell system also provides surgeons two methods of collecting bone marrow derived stem cells, either through the harvesting of stem cell aspirate with significantly higher stem cell counts (compared to standard bone marrow aspirate) or marrow-rich autograft dowels.

The DirectCell System provides surgeons the means to harvest tissue with high stem cell counts and combine it with a graft material that is actively involved in the cellular bone formation response, said Mark Borden, Biogennixs CTO. This results in an optimal biological graft that immediately begins the bone regeneration process.

Jeffrey Wang, chief of orthopaedic spine service at USC and co-director of the USC Spine Center (Los Angeles, USA), has been he using the product in his spine fusion cases. He commented: When you combine live cells with an advanced surface, you are optimising the healing response. Surgeons and hospitals alike need innovative solutions with strong scientific backing, which incorporate new biological technologies.

Biogennix CEO Chris MacDuff, added: As a company our strength has always been our focus and deep expertise in advanced bone regeneration technologies. I attribute the swift success of the DirectCell system primarily to the solid science supporting its benefits.

When you use the patients own cells, you completely eliminate the risk of disease transmission that has recently been seen with cadaver-based stem cell products. The DirectCell system not only enables the harvest of significantly higher cell counts, but it is a safer and significantly more cost-effective alternative.

See more here:
Biogennix's DirectCell advanced bone grafting system used in 500th case - Spinal News International

Bone Marrow Stem Cells Comments Off on Biogennix’s DirectCell advanced bone grafting system used in 500th case – Spinal News International | May 29th, 2022

Therunt-related transcription factor 1 (RUNX1) gene is known as a critical regulator of embryogenesis and definitive hematopoiesis in vertebrates, playing a vital role in the generation of hematopoietic stem cells (HSCs) and their differentiation into the myeloid and lymphoid lineage. The discovery of RUNX1 mutationsas the cause of familial platelet disorder (FPD) was pivotal to understanding the implications of this gene in hematological malignancies.FPD is an inherited bone marrow failure syndrome (IBMFS) with quantitative and qualitative platelet abnormalities and a highpredisposition to acute myeloid leukemia (AML)[1,2].IBMFS are genetic disorders characterized by cytopenia and hypoproliferation of one or more cell lineages in the bone marrow[1]. The production of blood cells (erythrocytes, granulocytes, and platelets) is compromised because of the mono-allelic gene mutation in one of certain bone marrow genes. Besides FPD, the other most common IBMFSs include Fanconi anemia (FA), Diamond-Blackfan anemia (DBA), Shwachman-Diamond syndrome (SDS), and severe congenital neutropenia (SCN)[3]. Patients with IBMFSs show a predisposition to developinghematological complications, such as myelodysplastic syndrome (MDS) or AML[3]. MDS is a pre-leukemic state defined by the presence of refractory cytopenia or refractory cytopenia with an excess of blasts (5-29%) in the bone marrow. AML is a blood cancer that is characterized by rapid leukemic blast cell growth and the presence of more than 30% myeloid blasts in the bone marrow[2].

Recent studies have shown that RUNX1 germline mutations in patients with IBMFS arelikeacquiredorsomatic RUNX1 mutations that were found in myeloid malignancies, particularly in MDS and AML[3].It has become clear that somatic RUNX1 mutations are more prevalent in MDS/AML that is secondary to IBMFS, such as FA and SCN. Unlike acquired MDS/AML, these forms of secondary MDS/AML are often refractory to treatment,resulting ina poor prognosis. Because the somatic mutation of RUNX1 was first identified in MDS and AML, RUNX1 has become known to be one of the most frequently mutated genes in a variety of hematologicalmalignancies[4].

Despite recent research having demonstrated the strong association of RUNX1 mutations in a variety of hematological malignancies, it is unclear howRUNX1 mutations contributetothepathogenesis of hematological malignancies in IBMFS. What are the frequencies of different RUNX1 mutations in various subgroups of hematological malignancies, as well as their impact on prognosis? Furthermore, is there any potential for the developmentof new cancer therapies following recent findings regarding the role of RUNX1 in the malignanttransformation[5]?

In this article, we summarize new research onthe role of RUNX1 mutations, published in February 2020 by three different groups[6-8].They performed different experiments in human, mouse, and induced pluripotent stem cell (iPSC) models to decipher the role of the RUNX1 gene in the malignant transformation of IBMFS; the mechanisms of pathogenesis; clinical and molecular characteristics of RUNX1 mutations; and the potential for the treatmentof cancers. The mouse and iPSC models suggested that secondary RUNX1 mutations in clones with granulocyte colony-stimulating factor 3 receptor (GCSF3R) mutations are weakly leukemogenic and that an additional clonal mutation in theCXXC finger protein 4 (CXXC4) gene is required for the full transformation to AML[9].Mutations in the CXXC4 gene lead to the hyperproduction of inflammatory proteins called theten-eleven translocation (TET2) proteins.This inflammation, in combination with the RUNX1 mutations, drives the development of myeloid malignancies[10].The other pathogenic mechanisms wherein RUNX1 mutations may initiate tumor cellproliferation 18arethe inhibition of the p53 pathway and hypermethylation of the promoter of Wingless and Int1 (WNT) inhibitor gene called secreted frizzled-related protein 2 (SFRP2)[11,12].

These discoveries may have the potential to aidthe development of new therapeutic strategies.Specifically, immunotherapy may be employed for suppression of the excessive immune response to hyperproduction of TET2 proteins.The other potential therapeutics, such as mouse double minute 2 (MDM2) andpoly adenosine diphosphate-ribose polymerase(PARP) inhibitors, may be used to inhibit the hyperactivation of the p53 pathway or hypersensitivity to DNA damage resulting from RUNX1 mutations[11]. Because the presence of RUNX1 mutation represents a poor prognostic factor in patients with MDS or AML, the investigation of various biomarkers is critical as they may detect the clones with RUNX1 mutation, in the early stages of leukemic progression[7].

Search Strategy

The PubMed online database search was used to select the articles which are included in this review. The findings were reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The following medical subject heading (MeSH) parameters were used: inherited and bone marrow and failure and syndromes. This search resulted in 5,051 articles.

Selection Criteria

The identified articles were further filtered. Thereview selectedonly articles that met the following criteria: (1) papers published between January and December 2020; (2) free full-text available; (3) papers written in English; and (4) studies conducted on human participants. Among screened articles, only clinical trials, meta-analyses, randomized controlled trials, and systematic reviews were included. Five citations from other sources were not included because they were not relevant to the topic. To further select the articles, we included the following MeSH terms: hematologic neoplasms, gene expression regulation, leukemic, RUNX1 protein, human, and Neutropenia, Severe Congenital, Autosomal recessive. Any articles that were not relevant to the role of the RUNX1 gene were excluded. These criteria allowcomparison between articles; however, it should be noted that differing lab protocols between studies prevents validation of results using the same assessment tool. A systematic search review is reported using the PRISMA 2020 guidelines [13].The diagram is presented in Figure1.

The selected articles were used to evaluate the clinical and molecular characteristics of RUNX1 mutation in various types of hematological malignancies, the mechanisms of pathogenesis caused by RUNX1 mutations, and potential therapeutic strategies for hematological malignancies with RUNX1 mutations.

Clinical and Molecular Characteristics of RUNX1 Mutation in Hematological Malignancies

RUNX1 gene has multiple biological functions in the human body. It regulates hematopoiesis, the cell cycle and genome stability, the p53 signaling pathway, apoptosis, and ribosomal biogenesis. During hematopoiesis, this gene controls the development of HSCs and their differentiation in different lineages. The transition from the G1-S to the G2/M phase of the cell cycle is facilitated by RUNX1. This gene controls cellular proliferation and differentiation via direct regulation of transcription, achieved by binding promoters of the genes that are encoding ribosomal RNA/proteins. According to recently published data, somatic mutations of RUNX1 were observed in various types of hematological malignancies. We present the frequency of RUNX1 mutations in various types of hematological malignancies in Table 1 below.

Most frequently, somatic mutations of RUNX1 were associated with the development of myeloproliferative neoplasm (MPN) (10.3-37.5%) and chronic myelomonocytic leukemia (CMML) (32.1-37%). Despite this, the association between RUNX1 somatic mutations and MDS was only 10%.

The Mechanisms of Pathogenesis Caused by RUNX1 Mutations

In the selected studies, the different mechanisms of pathogenesis caused by RUNX1 mutations were characterized. It has been shown that loss of RUNX1 function causes inhibition of differentiation of HSCs. Therefore, in pre-leukemia, we found expansion of HSCs and progenitor cells. RUNX1 mutations may attenuate the G1-S phase and enhance the proliferation of hematopoietic cells that occur during the mitotic phase of the cell cycle (G2/M) [7]. The mutations can also result in genomic instability, leading to increased DNA damage and impaired DNA repair. Some mutations in RUNX1 are associated with alterations of signaling pathways, such as WNT and p53. Hypermethylation of the WNT inhibitor gene promoter, SFRP2, can lead to aberrant activation of the WNT signaling pathway and leukemogenesis in AML. When functioning normally, the RUNX1 gene acts to increase transcriptional activity of the p53 signaling pathway, in response to DNA damage caused by exposure to different agents such as chemicals, radiation, and toxins. Mutations in RUNX1 may lead to defects in p53-mediated apoptosis/DNA repair/cell cycle regulation resulting in tumorigenesis. Furthermore, loss-of-function mutations of RUNX1 may aid tumor-initiating cells in hematological malignancies via inhibition of p53 signaling and apoptosis, among other mechanisms. Such mutations have reduced ribosomal biogenesis in HSCs and directed to malignant proliferative processes in the pre-leukemic stage [6]. In vivo studies, administration of amino acid L-leucine to patients with DBA resulted in loss-of-function mutations in ribosomal protein genes. Research into iPSC confirmed that the introduction of the mutated RUNX1 gene into CD34+CD45+ cells via lentivirus can stimulate receptor which binds the granulocyte colony-stimulating factor 3 receptor (GCSF3R) and initiates the production of immature cells. The percentage of immature cells was significantly increased when compared to the percentage in empty vector (ev) control studies. The myeloid differentiation of GCSF3R-d715/RUNX1-D171N and GCSF3R-d715/ev cells without RUNX1-D171N lentiviral expression vector or with an ev is presented in Figure 2.

Potential Therapeutic Strategies for RUNX1-Mutated Cases of Hematological Malignancies

Clinical trials demonstrated potential therapeutic strategies for RUNX1 mutated hematologic malignancies.Based on the current RUNX1 roles in human hematopoiesis, various therapeutic options were developed. Thus far, the different DNA repair inhibitors can be useful in the M phase of cell cycle repair or bypassing the cells with damage because RUNX1 mutations lead to DNA damage and impaired DNA repair[32].In addition, adriamycin as an antineoplastic drug can stimulate the RUNX1-p53 complex which is important in the activation of p53-mediated apoptosis[11].L-leucine can be used to improve anemia in the genetic DBA mouse models and DBA patients. This agent is a potent stimulator of protein translation that is initialized by the activation of the mammalian target of rapamycin (mTOR) protein kinase. This kinase stimulates protein synthesis[33].Another agent, clustered regulatory interspaced short palindromic repeats-associated genes (CRISPR-Cas) can be used as a genomic targeted treatment as this agent can edit the RUNX1 gene by cutting pieces of DNA where RUNX1 mutations are, followed by stimulating natural DNArepair[6].Finally, hypoxia-inducible factor 1 (HIF-1) inhibitor can potentially treat various hematological malignancies as a modulator of cell metabolism. MDS and other hematological malignancies are in hypoxia-like status and produce their energy through the tricarboxylic acid (TCA) cycle. The use of HIF-1 inhibitor can suppress the TCA cycle and modulate it into an aerobic metabolic pathway called glycolysis through which the normal cells are supplied with energy. The recent studies proposed therapeutic strategies that employed the different pathophysiological mechanisms to correct the RUNX1 mutations, as shown in Figure3.

The RUNX1 gene plays essential roles in a wide range of biological processes, including the development of HSCs, cell proliferation,megakaryocyte maturation, T lymphocyte-lineage differentiation,and apoptosis. It is not surprising that RUNX1 dysfunction is associated with the development of IBMFSs and various hematological malignancies[7,21,34].

Previous studies have shown that RUNX1 is one of the most frequently mutated genes in hematologicalmalignancies. RUNX1mutations account for about 10-15% of all somatic mutations that have been detected in MDS[21,35].The incidence of RUNX1 mutations in CMML and chronic myelogenous leukemia (CML) is even higher, ranging from 32.1% to 37%, respectively[36].RUNX1 mutations have also been reported in 14% of patients withMPN,15.6% of patients with acute lymphoblastic leukemia (ALL),and 10.3-37.5% of AML patients. Importantly, these studies have shown that mutated RUNX1can be used as an independent prognostic factor for event-freesurvival (EFS), relapse-free survival (RFS), or overall survival (OS) in hematological malignancies[37].Therefore, AML patients with RUNX1 mutations had worse prognosis, resistance to chemotherapy, and inferior EFS,RFS, and OS. Reduced OS was also observed in high-risk MDS patients with RUNX1mutations who had poor clinical outcomes and shorter latency for progression to secondary AML[38,39].

Little is known about the role of the RUNX1 gene in the development of secondary somatic mutations in patients with IBMFSs and how these mutations lead to hematological malignancies. The data have shown that individuals with IBMFSs, such as FPD and FA, have a high lifetime risk (30-44%) of developing MDS and AML [29,30]. Among FA-associated MDS or MDS/AML patients, RUNX1 mutations were detected in the range from 20.7% to 31.25%, respectively. In SCN-MDS/AML patients RUNX1 mutations were seen at the highest rate of up to 64.5% which revealed that these types of mutations are the most frequent somatic secondary mutations in SCN-MDS/AML [31,40,41]. Given that the patients with SCN are more prone to develop somatic RUNX1 mutations, SCN/AML has been recognized as an important model to further investigate the role of secondary RUNX1 mutations in the molecular pathogenesis of hematological malignancies. SCN is an IBMFS classified by severe neutropenia and life-threatening infections such as fungal infections or bacterial sepsis [40]. The most frequent mutated gene is encoding neutrophil elastase (ELANE). The treatment consists of life-long administration of GCSF3 that successfully alleviates the neutrophil counts [42]. As is common with other forms of IBMFSs, SCN patients have a high risk of developing MDS or AML. The incidence of developing MDS or AML directly correlates to the number of years on GCSF3. Therefore, after 15 years on GCSF3, the incidence of developing MDS or AML is 21% [31]. The majority of SCN patients with leukemic progression develop hematopoietic clones with somatic mutations in GCSF3R, resulting in a truncated form of GCSF3R [42]. It is important to note that these clones can persist for several months or years before MDS or AML becomes symptomatic, raising the question of how these GCSF3R mutants contribute to the malignant transformation of SCN [31,41]. Given this, a mouse model was used to study the role of RUNX1. In this study, a truncated GCSF3R (GCSF3R-D715) identical to the mutant GCSF3R form in SCN patients was expressed in mice [43]. In addition, a lentiviral expression vector was used to express RUNX1-mutant D171N in conjunction with an enhanced green fluorescent protein (eGFP) [8]. The mouse bone marrow (BM) cells with expressed GCSF3R-D715 mutation were subsequently serially transplanted into wild-type recipients. Before transplantation, the recipients were treated either three times per week with GCSF3 or with peripheral blood solvent (PBS) control. Primary recipients who were treated with GCSF3 and transplanted with GCSFR3-RUNX1-mutant BM cells developed myeloblasts in peripheral blood (PB) that were sustained for at least 30 weeks. None of these mice developed symptoms of AML, suggesting that the elevated myeloblasts in the PB reflected a pre-leukemic state rather than a fully transformed state. However, upon transplantation in secondary and tertiary recipients, mice developed GCSF3R-RUNX1-mutant AML. Whole-exome sequencing (WES) was performed on lin-c-kit (LK) cells and revealed that AML cells from the secondary and tertiary recipients had seven-fold higher expressions of CXXC4 mutations than the cells from the primary recipient. Recently, CXXC4 mutations have also been detected in human AML cases [9]. It seems that CXXC4 mutations enhance the production of TET2 protein which is known to be an inflammatory factor and has a similar role to interferon-gamma, interleukin-6, and others. Interferon-gamma and interleukin-6 are cytokines that are produced in response to infections and tissue damage, with pro- and anti-inflammatory effects. Hyperproduction of TET2 leads to inflammatory processes that may play an important role in the development of myeloid malignancy involving RUNX1 mutations [10]. In conclusion, isolated RUNX-Runt homology domain (RHD) mutations are only weakly leukemogenic and an additional clonal mutation that reduces levels of TET2 is what drives the full transformation to AML [8,32]. The data suggest the need for further investigation into the somatic RUNX1 mutations in HSPCs that already harbour a GCSF3R nonsense mutation. To achieve this, a CRISPR/Cas9-based strategy was used to introduce a patient-derived GCSF3R nonsense mutation into iPSC. CRISPR-Cas9 is a technology used for removing, adding, or altering sections of the DNA. After culturing iPSC, CD34+CD45+ cells were transduced using a lentivirus to express the RUNX1-RHD D171N mutant. The experiments confirm that the combinations of GCSF3R and RUNX1 mutations have a moderate effect on myeloid differentiation and result in an increasing number of myeloblasts. These findings corroborate the findings in the mouse model and suggest that secondary RUNX1 mutations in clones with GCSF3R mutations are not sufficient to fully transform to AML.

Most of the RUNX1 mutations are mono-allelic, such as in FPD, an IBMFS resulting in apredisposition to leukemia[1,2]. Germline RUNX1 mutations are dominant-negative mutations and correlate toa higher risk of developing hematological malignancies compared to RUNX1 loss-of-function mutations[5-8].It is important to note, however, that such germline mutations alone are not sufficient for the development of leukemia and additional mutations in RUNX1 (bi-allelicmutations)or epigenetic modifiers, splicing factors, or tumor suppressors are required to induce myeloid malignancies[1,4].

It has been observed that mutations in RUNX1 are associated with alterations of p53 and other signaling pathways, such as WNT, bone morphogenetic proteins (BMP), transforming growth factor-beta (TGF-), rat sarcoma-the extracellular signal-regulated kinase (RAS-ERK), Hippo-yes-1-associated protein (YAP1), and Notch.Unlike mono-allelic mutations, loss-of-function mutations of RUNX1 are responsible for initiating tumor cell proliferation by inhibiting the p53 signaling pathway and apoptosis.Thep53 pathway is activated in DNA damage and is responsible for DNA repair.RUNX1 increases the transcriptional activity of p53, potentially via up-regulation of p300-mediated acetylation of p53. RUNX1 mutations lead to a reduction of p53-mediated apoptosis[11].The WNT pathway is important for cellular proliferation and differentiation, with aberrant activation of this pathway being reported in various tumors. RUNX1 mutations were closely associated with hypermethylation of the promoter of one of the WNT inhibitor genes (SFRP2) in AML. It was suggested that the WNT inhibitor hypermethylation might lead to aberrant activation of the WNT signaling pathway. It is suggested that mutation in the RUNX1 gene can interact with the SFRP2 gene which is known as an inhibitor gene responsible for the suppression of the WNT signaling pathway. Due to interaction with genetic alterations, the hypermethylation of SFRP2 gene promoter is initiated and leads to leukemogenesis where cellular proliferation and differentiation are uncontrolled[12].

This review has highlighted the importance of studying the role of somatic RUNX1 mutations in the pathogenesis of hematological malignancies and the potential implications in the development of oncological therapies. This review does, however, had some limitations.First,the results presented in this review were collected from only three articles that were published over the limited time frame of one year. In addition, we included only articles that were available in the PubMed database and in both free text format and English language. This review did not apply the same assessment tools such as the lab protocols for conducting experiments. Variations between lab protocols did not allow the comparison of study results. In all the articles included, the scope of the study was the role of RUNX1 mutations in animal and human disease models, including only SCN and FA as the IBMFS representatives without knowing if RUNX1 mutations may contribute to the development of malignancies in other IBMFS. A broader literature search and greater inclusion of studies about RUNX1 mutations in pathogenesis in other IBMFS may better represent and validate the inferences from this review.

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A Systematic Review of the Role of Runt-Related Transcription Factor 1 (RUNX1) in the Pathogenesis of Hematological Malignancies in Patients With...

Bone Marrow Stem Cells Comments Off on A Systematic Review of the Role of Runt-Related Transcription Factor 1 (RUNX1) in the Pathogenesis of Hematological Malignancies in Patients With… | May 29th, 2022

The new report by Expert Market Research titled, Global Stem Cell Banking Market Report and Forecast 2021-2026, gives an in-depth analysis of the globalstem cell banking market, assessing the market based on its segments like Service type, product type, utilisation, bank type, application, and major regions like Asia Pacific, Europe, North America, Middle East and Africa and Latin America. The report tracks the latest trends in the industry and studies their impact on the overall market. It also assesses the market dynamics, covering the key demand and price indicators, along with analysing the market based on the SWOT and Porters Five Forces models.

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The key highlights of the report include:

Market Overview (2021-2026)

The global stem cell bank market is primarily driven by the advancements in the field of medicine and the rising prevalence of genetic and degenerativediseases. Further, the increasing research and development of more effective technologies for better preservation, processing, and storage of stem cells are aiding the growth. Additionally, rising prevalence of chronic diseases globally is increasing the for advances inmedicaltechnologies, thus pushing the growth further. Moreover, factors such as rising health awareness, developinghealthcare infrastructure, growing geriatric population, and the inflatingdisposableincomes are expected to propel the market in the forecast period.

Industry Definition and Major Segments

Stem cells are undifferentiated cells present in bone marrow,umbilical cordadipose tissue and blood. They have the ability to of differentiate and regenerate. The process of storing and preserving these cells for various application such as gene therapy, regenerative medicine and tissue engineering is known as stem cell banking.

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By service type, the market is divided into:

Based on product type, the industry can be segmented into:

The market is bifurcated based on utilization into:

By bank type, the industry can be broadly categorized into:

Based on application, the industry can be segmented into:

On the basis of regional markets, the industry is divided into:

1 North America1.1 United States of America1.2 Canada2 Europe2.1 Germany2.2 United Kingdom2.3 France2.4 Italy2.5 Others3 Asia Pacific3.1 China3.2 Japan3.3 India3.4 ASEAN3.5 Others4 Latin America4.1 Brazil4.2 Argentina4.3 Mexico4.4 Others5 Middle East & Africa5.1 Saudi Arabia5.2 United Arab Emirates5.3 Nigeria5.4 South Africa5.5 Others

Market Trends

Regionally, North America is projected to dominate the global stem cell bank market and expand at a significant rate. This can be attributed to increasing research and development for stem cell application in various medical fields. Further, growing investments of pharmaceutical players and development infrastructure are other factors that are expected to stem cell bank market in the region. Meanwhile, Asia Pacific market is also expected to witness fast growth owing to the rapid development in healthcare facilities and increasing awareness of stem cell banking in countries such as China, India, and Indonesia.

Key Market Players

The major players in the market are Cryo-Cell International, Inc., Smart Cells International Ltd., CSG-BIO Company, Inc., CBR Systems Inc., ViaCord, LLC, LifeCell International Pvt. Ltd., and a few others. The report covers the market shares, capacities, plant turnarounds, expansions, investments and mergers and acquisitions, among other latest developments of these market players.

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Expert Market Research is a leading business intelligence firm, providing custom and syndicated market reports along with consultancy services for our clients. We serve a wide client base ranging from Fortune 1000 companies to small and medium enterprises. Our reports cover over 100 industries across established and emerging markets researched by our skilled analysts who track the latest economic, demographic, trade and market data globally.

At Expert Market Research, we tailor our approach according to our clients needs and preferences, providing them with valuable, actionable and up-to-date insights into the market, thus, helping them realize their optimum growth potential. We offer market intelligence across a range of industry verticals which include Pharmaceuticals, Food and Beverage, Technology, Retail, Chemical and Materials, Energy and Mining, Packaging and Agriculture.

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Global Stem Cell Banking Market To Be Driven At A CAGR Of 13.5% In The Forecast Period Of 2021-2026 ManufactureLink - ManufactureLink

Bone Marrow Stem Cells Comments Off on Global Stem Cell Banking Market To Be Driven At A CAGR Of 13.5% In The Forecast Period Of 2021-2026 ManufactureLink – ManufactureLink | May 29th, 2022

The latest release titled Rheumatoid Arthritis Stem Cell Therapy Market Research Report 2022-2028 (by Product Type, End-User / Application, and Regions / Countries) provides an in-depth assessment of the Rheumatoid Arthritis Stem Cell Therapy including key market trends, upcoming technologies, industry drivers, challenges, regulatory policies, key players company profiles, and strategies. Global Rheumatoid Arthritis Stem Cell Therapy Market study with 100+ market data Tables, Pie Chat, Graphs & Figures is now released. The report presents a complete assessment of the Market covering future trends, current growth factors, attentive opinions, facts, and industry-validated market data forecast until 2028.

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Global Rheumatoid Arthritis Stem Cell Therapy Market and Competitive Analysis:

Know your current market situation! Not only an important element for new products but also for current products given the ever-changing market dynamics. The study allows marketers to stay in touch with current consumer trends and segments where they can face a rapid market share drop. Discover who you really compete against in the marketplace, with Market Share Analysis know market position, % Market Share, and Segmented Revenue of Rheumatoid Arthritis Stem Cell Therapy Market.

Moreover, it will also include the opportunities available in micro markets for stakeholders to invest, a detailed analysis of the competitive landscape, and product services of key players. Analysis of Rheumatoid Arthritis Stem Cell Therapy companies, key tactics followed by Leading Key Players:

Mesoblast, Roslin Cells, Regeneus, ReNeuron Group, International Stem Cell Corporation, Takeda

Market Segments by Type:

Allogeneic Mesenchymal Stem Cells, Bone Marrow Transplant, Adipose Tissue Stem Cells

Market Segments by Application:

Hospitals, Ambulatory Surgical Centers, Specialty Clinics

The base on geography, the Rheumatoid Arthritis Stem Cell Therapy market has been segmented as follows:

North America includes the United States, Canada, and MexicoEurope includes Germany, France, the UK, Italy, SpainSouth America includes Colombia, Argentina, Nigeria, and ChileThe Asia Pacific includes Japan, China, Korea, India, Saudi Arabia, and Southeast Asia

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The Study Objectives are:

A comprehensive insight into key players operating in the Rheumatoid Arthritis Stem Cell Therapy market and their corresponding data. It includes product portfolio, annual revenue, expenditure on research and development, geographical presence, key developments in recent years, and growth strategies. Regional analysis, which includes insight into the dominant market and corresponding market share. It also includes various socio-economic factors affecting the evolution of the market in the region. The report offers a comprehensive insight into different individuals from value chains such as raw materials suppliers, distributors, and stockholders.

Key Opportunities:

The report examines the key opportunities available in the Rheumatoid Arthritis Stem Cell Therapy market and outlines the factors that are and will be driving the growth of the industry. It considers the previous growth patterns, the growth drivers, and the current and future trends.

Pricing and Forecast

Pricing/subscription always plays an important role in buying decisions; so we have analyzed pricing to determine how customers or businesses evaluate it not just in relation to other product offerings by competitors but also with immediate substitute products. In addition to future sales Separate Chapters on Cost Analysis, Labor*, production*, and Capacity are Covered.

(Note: * if Applicable)

Key Questions Answered:

1. What is the market size and CAGR of the Rheumatoid Arthritis Stem Cell Therapy market during the forecast period?2. How is the growing demand impacting the growth of Rheumatoid Arthritis Stem Cell Therapy market shares?3. What is the growing demand of the Rheumatoid Arthritis Stem Cell Therapy market during the forecast period?4. Who are the leading vendors in the market and what are their market shares?5. What is the impact of the COVID-19 pandemic on the APAC Rheumatoid Arthritis Stem Cell Therapy market?

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Rheumatoid Arthritis Stem Cell Therapy Market Growth: 2022, Observing High Industry Demand and Business Trends Carbon Valley Farmer and Miner -...

Bone Marrow Stem Cells Comments Off on Rheumatoid Arthritis Stem Cell Therapy Market Growth: 2022, Observing High Industry Demand and Business Trends Carbon Valley Farmer and Miner -… | May 29th, 2022