Stem Cells Market is expected to reach US$270.5 billion by 2025, TMR – BioSpace

The global stem cells market is predicted to witness players seeking funds from international organizations for developing new therapies. With a view to cement their position in the market, players could take to the adoption of partnerships and collaborations with pharmas. This could also help them to expand their product portfolios. While these factors are expected to enhance market growth, there could be a few others helping with strong demand for stem cells.

Transparency Market Research (TMR) foresees the global stem cells market to earn a US$270.5 bn by the completion of 2025 while registering a 13.8% CAGR for the forecast tenure 2017-2025. In a research led by University of Singapores (NUS) Professor G.V. Shivashankar and the FIRC Institute of Molecular Oncology (IFOM), it has been found that mature cells can be confined to reprogram them into re-deployable stem cells. Interestingly, this could be achieved without direct genetic modification.

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Induced Pluripotent Stem Cells as Emerging Segment of Market

There are various types of products available in the global stem cells market: induced pluripotent, human embryonic, and adult stem cells. Among these, the market could find adult stem cells collecting a larger share in the coming years. Their demand could increase due to their potential to multiply into trillions of specialized cells capable of repairing tissue damage and lowering the risk of rejection.

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North America Banks on Massive Investments to Lead Market

On the regional front, the global stem cells market is prognosticated to find North America taking a leading position in the near future. By the end of the forecast period, the region could earn US$167.3 bn. The following factors are anticipated to augur well for the regional market.

North America could be trailed by Europe during the course of the forecast period. Medical tourism in European countries such as Germany could push the growth of the market in the region. Germany welcomes patients from the U.S., Canada, and even other countries. On the other hand Asia Pacific is expected to grow at a faster CAGR of 14.6%.

Some of the key players operating in the global stem cells market are STEMCELL Technologies Inc., Astellas Pharma Inc., Cellular Engineering Technologies Inc., BioTime Inc., Takara Bio Inc., U.S. Stem Cell, Inc., BrainStorm Cell Therapeutics Inc., Cytori Therapeutics, Inc., Osiris Therapeutics, Inc., and Caladrius Biosciences, Inc.

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Stem Cells Market is expected to reach US$270.5 billion by 2025, TMR - BioSpace

New sickle cell disease treatments are helping people live longer and giving them a higher quality of life – PhillyVoice.com

Treatment for sickle cell disease has come a long way since the 1970s when the life expectancy of people living with it was less than 20 years.

People with sickle cell disease are not only living longer life expectancy is now 42 to 47 years of age but are enjoying a better quality of life, too.

"In the Philadelphia area, there has been great pediatric care for sickle cells disease and because of that people who have it are living very well," said Dr. Farzana Sayani, a hematologist at Penn Medicine.

Sayani is the director of a comprehensive sickle cell program focusing on adults living with the disease. Penn also has an active transition program for youth transitioning from a pediatric institution to adult care.

Sickle cell disease is an inherited red blood cell disorder that affects about 100,000 Americans.It is most often found in people of African or Hispanic descent.About 1 in 365 African-American babies are born with sickle cell disease, according to Sayani.

People who have the disease inherit an abnormal type of hemoglobin in their red blood cells, called Hemoglobin S, from both their mother and father.When only one parent has the hemoglobin S gene, a child will have the sickle cell trait, but usually does not develop the disease. But they may pass it on to their children.

Hemoglobin is the protein in the blood responsible for carrying oxygen to the rest of the body. Hemoglobin S causes red blood cells to become stiff and sickle-shaped. Instead of being round in shape, they look like crescent moons.

Sickle cells are sticky and can bind together, blocking the flow of blood and preventing oxygen from getting where it needs to go in the body. This causes sudden attacks of pain referred to as a pain crisis.

There are severaldifferent types of sickle cell disease.Hemoglobin SS, also known as sickle cell anemia, is the most common and most severe type of sickle cell disease.

Anemia occurs when red blood cells die at a rate faster than the body can replace them. Normal red blood cells generally live for 90 to 120 days. Sickled cells only live for 10 to 20 days. This shorter life-to-death cycle is harder for the body to sustain.

Another form,Hemoglobin SC, is not as severe as sickle cell anemia, but it can still cause significant complications, Sayani said.Other forms include Hemoglobin S0 thalassemia, Hemoglobin S+ thalassemia, Hemoglobin SD and Hemoglobin SE.

Sickle cell disease screening is a mandatory part of newborn screenings in Pennsylvania.

If the screening is positive, the family is informed and plugged into the health care system in order to receive the proper care.

If the disease is not diagnosed at birth, a blood test can confirm it at any age in which symptoms start to surface.

The severity of sickle cell disease can vary.

Each individual is affected differently, making it difficult to predict who will get what complications, Sayani said. That is why a comprehensive sickle cell program is so important.

Early signs include a yellowish tint to the skin or jaundice, fatigue and a painful swelling of the hands and feet.

"Young children with sickle cell disease may be tired, not eat very well and have delayed growth," Sayani said. "They may also develop anemia, be at greater risk of infection and start to experience pain crises."

Acute pain crises, also known as vaso-occlusive crises, can lead to long stays in the hospital to manage the crippling pain. Children with sickle cell disease also tend to experience delayed growth and puberty.

As a person with sickle cell disease grows older, the sickled red blood cells start to affect various organs, bones and joints.

This can lead to acute chest syndrome, which occurs when damaged lung tissues makes it difficult to breathe. Brain complications, including stroke, are possible.People with sickle cell disease are also prone to heart damage, eye problems, and infections like chlamydia, salmonella and staphylococcus. Chronic and acute pain is common.

There are different types of medicine that can help manage sickle cell disease.

Last year, an oral medicine was approved that makes sickle cells less likely to sickle. So was an intravenous medicine that has been shown to reduce pain crises and hospitalizations by 50%. Some people living with sickle cell disease also may need regular blood transfusions.

Hydroxyurea has also been used successfully for many years to reduce pain crises and the need for blood transfusions and hospitalizations.

Currently, blood and bone marrow transplant is the only way to cure the disease. But it is not an option for everyone because of the difficulty of finding a well-matched stem cell donor.

A related donor is best but only about a third of sickle cell patients have a donor that is related and fully-matched, Sayani said.

While these transplants have a 85% or more success rate, they also are associated with significant risks, including organ dysfunction, infection and graft vs. host disease which can be quite debilitating.

Transplants completed in children have the best results, Sayani said. But because of the risks involved, doctors only suggest it for patients with severe forms of the disease.

Early clinical trials with gene therapy are also showing promise, she added.

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New sickle cell disease treatments are helping people live longer and giving them a higher quality of life - PhillyVoice.com

Olive Oil Consumption Could Lead to a ‘Younger Brain’ in the Elderly, Researchers Say – Olive Oil Times

As people age, the more their brains could benefit from the action of an important component in olive oil.

New research has revealed the deeper effects of hydroxytyrosol (HTyr): Not only does it protect brain functions from aging, but it may even restore the vitality of brain neurons, and multiply them.

Italian scientists at the National Research Center (CNR) investigated how hydroxytyrosol works in those portions of the brain that generate new neurons throughout life. They discovered that HTyr impacts brain activities far beyond its well-known neuroprotective effects.

Researchers at the CNR Biochemistry and Cellular biology Lab (CNR-Ibbc) were able to show how the administration of the compound in the elderly may reverse neuronal aging, combining the protection of the active neurons and the generation of new ones.

Hydroxytyrosol oral consumption by young and older animals within amonth shows not only how the new neurons generated by the brain in that timeframe are protected, but it also hints how in older animals it stimulates the multiplication of stem cells, said Felice Tirone, chief scientist and author of the study published in Faseb Journal. It is from those cells that new neurons are generated.

Tirone and his colleagues explained that HTyr activates neurogenesis in the dentate gyrus of an adult, where new neurons are generated, by increasing survival of new neurons and decreasing apoptosis. The neurons multiplication effect is only found in aged brains.

We also found how the antioxidant activity of hydroxytyrosol activates asort of cleaning treatment for nervous cells, in the sense that it washes away several byproducts of brain aging like the lipofuscin, which are debris found in neuron cells, Tirone explained.

The whole array of these effects hints at the possibility of reversing some of the most known effects of brain aging.

Olive oil is at the core of the Mediterranean diet and, as often reported in these pages, its regular consumption has been scientifically linked to health improvements in humans of any age at every latitude.

The new research hints at anew series of products that could help to relieve the reduction of cognitive abilities in aging humans.

CNR scientists underlined in apress statement that hydroxytyrosol is not only found in olive oils people usually consume but also in the byproducts of olive oil production.

That process impacts on the environment, but the biological waste it produces holds great quantities of hydroxytyrosol. By upgrading procedures and means, by splitting the good compounds from the other byproducts, oil mills could obtain hydroxytyrosol while also reducing the environmental impact of their activities, said Tirone.

The CNR statement explained that scientists could verify how the new neurons produced in the brain of the aged individuals actually enter the neuronal circuits and fuel neuronal functionality.

The daily intake of the compound in our study is similar to the dose ahuman could ingest with an enriched diet or food integrators. Still, the most efficient intake of hydroxytyrosol would happen through olive oil consumption, said Laura Micheli, one of the CNR-Ibbc researchers who signed the study.

Scientists also explained that future research will have to verify the behavioral effects of the increased neuron production and the extent of the HTyr treatment of neural aging.

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Olive Oil Consumption Could Lead to a 'Younger Brain' in the Elderly, Researchers Say - Olive Oil Times

Proteostasis Therapeutics and CF Europe Announce Completion of Patient Enrollment for CHOICES, the First-Ever Personalized Medicine-Based Study in…

Ex Vivo Testing Phase Underway with Tissue Samples Collected from More than 500 Adult CF Patients; Enrollment Target Exceeded

Clinical Testing Phase to Begin in 2H 2020

Company Expects CHOICES to Potentially Serve as the Basis for an MAA in 2021

BOSTON, Feb. 24, 2020 /PRNewswire/ --Proteostasis Therapeutics, Inc. (NASDAQ:PTI), a clinical stage biopharmaceutical company dedicated to the discovery and development of groundbreaking therapies to treat cystic fibrosis (CF) and CF Europe, the federation of 48 national CF Associations in Europe, today announced the completion of enrollment of 502 patients with CF for HIT-CF, a European-based initiative that is paving the path to personalized medicine through the CHOICES clinical trial. CHOICES will test PTI drug combinations in an ex vivo study and then in a clinical trial to assess the predictability of the organoid assay for clinical benefit.

For the ex vivo portion, organoids derived from tissue samples provided by patients enrolled in the study are evaluated for responsiveness to investigational CFTR modulators, including Proteostasis' CFTR potentiator, corrector and amplifier, dirocaftor (DIR), posenacaftor (POS) and nesolicaftor (NES), respectively. Based on an individual's organoid response, patients will be invited to progress to the next portion of the study which is a placebo controlled, double blind, crossover study known as the CHOICES trial (Crossover trial based on Human Organoid Individual response in CF - Efficacy Study).

The results from CHOICES may serve as the basis for a potential Marketing Authorization Application with the European Medicines Agency (EMA) in 2021 through a novel regulatory pathway. This strategic initiative is led by the HIT-CF consortium, funded through the European Commission's Horizon 2020 program. The CHOICES clinical study is part of PTI's broader clinical development strategy for its CFTR modulator candidates that also includes the MORE trial in CF subjects with the most common F508del homozygous genotype.

"The enrollment of more than 500 patients across Europe in the first phase of the HIT-CF project is a testament to the strategic imperative this program holds for both the patient and treatment community," said Geoffrey Gilmartin, M.D., M.M.Sc., Chief Medical Officer of Proteostasis Therapeutics. "With the successful translation of activity from organoids to patients, this study has the potential to usher in a personalized medicine approach to CF. This approach would begin with patients who have less common mutations, but could ultimately serve the broader CF community by delivering personalized treatment choices that maximize benefit based on each patient's responsiveness to therapy."

"We are excited that Proteostasis is participating in the HIT-CF project and supporting our efforts to bring CF treatment to more people across Europe," said Jacquelien Noordhoek, President of CF Europe and representative of the Netherlands Cystic Fibrosis Society (NCFS). "Enrolled individuals are a portion of the approximately 2,300 adults in the European patient registry who are not eligible for any currently approved modulator due to their genotype and the HIT-CF project represents the only option to explore potential benefit of disease modifying drugs for this group. Putting patients with CF first is our highest priority. We are looking forward to continuing our partnerships and providing Europeans with CF the best possible care."

About Organoids

Organoids are cell cultures that grow in a culture dish with properties similar to those of the organ from which they are derived. Because organoids are made from stem cells, they contain the same mutations as the person from whom the biopsies are derived. Investigational drugs which target the basic defect of CF can be used in an organoid system to evaluate rare mutations where the drugs may have a positive effect.

Unlikein vitrosystems such as human bronchial epithelial (HBE) cells, which are derived from lungs that have been removed from CF patients, or the engineered rat-derived FRT cell line (which has had false positive clinical results), rectal organoids are cultured from tissues obtained through a minimally invasive and painless procedure from donors who then become eligible to participate in a clinical study. Organoids can provide valuable insights for donors, including their likelihood of achieving improvements in pulmonary function and reductions in sweat chloride concentration with CFTR modulators based on theex vivoresponse to those drugsi.

Story continues

About HIT-CF Europe

HIT-CF Europe is a research project which aims to provide better treatment and better lives for people with cystic fibrosis (CF) and rare mutations. To achieve this, drug candidates are first tested on patient-derived organoids in qualified laboratories acrossEurope. Subsequently, based on the measured signal in the organoids, a smaller group of patients will be invited to participate in clinical trials with investigational molecules from participating pharmaceutical companies.

All participating centers are part of theEuropean Cystic Fibrosis Society Clinical Trial Network (ECFS-CTN). The project has received funding from theEuropean Union'sHorizon 2020 research and innovation program under grant agreement number 755021. For more information, visitwww.hitcf.org.

About Proteostasis Therapeutics, Inc.

Proteostasis Therapeutics, Inc.is a clinical stage biopharmaceutical company developing small molecule therapeutics to treat cystic fibrosis and other diseases caused by dysfunctional protein processing. Headquartered inBoston, MA, theProteostasis Therapeuticsteam focuses on identifying therapies that restore protein function. For more information, visitwww.proteostasis.com.

Safe Harbor

This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including but not limited to statements regarding the potential of PTI drug combinations, expectations regarding ex vivotesting of our proprietary combinations in organoids and clinical evaluation in CF patients, the expected timing for enrollment, completion and reporting of results of our CHOICES Phase 3 clinical trial, our commitment to expanding available therapeutic options for CF patients and the intended goals of the CHOICES trial and the ability to serve as a potential basis for future marketing approval. Words such as "aim," "may," "will," "expect," "anticipate," "estimate," "intend," and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially from those expressed or implied by the forward-looking statements, and we, therefore cannot assure you that our plans, intentions, expectations or strategies will be attained or achieved. Such risks and uncertainties include, without limitation, the potential of our proprietary combination therapies for the treatment of CF, the potential benefit of our proprietary combination therapies to patients, expected completion of our clinical studies and cohorts for our clinical programs, initiation of a pivotal or registrational study, the possibility final or future results from our drug candidate trials (including, without limitation, longer duration studies) do not achieve positive results or are materially and negatively different from or not indicative of the preliminary results reported by the Company (noting that these results are based on a small number of patients and small data set), uncertainties inherent in the execution and completion of clinical trials (including, without limitation, the possibility that FDA or other regulatory agency comments delay, change or do not permit trial commencement, or intended label, or the FDA or other regulatory agency requires us to run cohorts sequentially or conduct additional cohorts or pre-clinical or clinical studies), in the enrollment of CF patients in our clinical trials in a competitive clinical environment, in the timing of availability of trial data, in the results of the clinical trials, in possible adverse events from our trials, in the actions of regulatory agencies, in the endorsement, if any, by therapeutic development arms of CF patient advocacy groups (and the maintenance thereof). For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our most recent Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission. We assume no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, unless required by law.

CONTACTS:

Investors:David Pitts / Claudia StyslingerArgot Partners212.600.1902david@argotpartners.com/ claudia@argotpartners.com

Media:David RosenArgot Partners212.600.1902david.rosen@argotpartners.com

HIT-CF Project Coordination:HIT-CF ConsortiumUniversity Medical Centre Utrecht (The Netherlands)HITCF@umcutrecht.nl

i Berkers et al, Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis Cell Reports 26, 17011708,February 12, 2019

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SOURCE Proteostasis Therapeutics, Inc.

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Proteostasis Therapeutics and CF Europe Announce Completion of Patient Enrollment for CHOICES, the First-Ever Personalized Medicine-Based Study in...

Transplant for Szary Syndrome is Patient’s First Step in Returning to the Dance Floor – Dana-Farber Cancer Institute

The first time Bill Cronin Googled his own cancer diagnosis in 2016, his heart sank. He had Szary syndrome, a rare and aggressive form of cutaneous T-cell lymphoma and staring back at him were countless articles predicting a negative prognosis.

However, after receiving a stem-cell transplant at Dana-Farber/Brigham and Womens Cancer Center, Cronin is returning to the life he enjoyed before cancer.

Im at a place I never thought Id get to, Cronin says.

In 2015, Cronin, then 60, started feeling incredibly itchy and developed an accompanying rash. He went to his dermatologist, who diagnosed him with eczema and told him to return in five months. The rash continued to grow, however, and at the five month mark, Cronins dermatologist encouraged him to undergo further testing at Dana-Farber.

A blood test revealed that Cronins T-cells a type ofwhite blood cells that make up part of the immune system had becomecancerous. In the case of Szary syndrome, lymphoma cells will circulatethrough the blood stream and deposit in different areas of the skin. This willgenerally lead to a full-body rash and intense itchiness.

Cronin would need a stem cell transplant to combat the disease, but before he could receive one, his care team had to get him into remission. Patients who do not achieve remission prior to transplant have a high chance of relapsing.

When they first told me everything, I was really scared, says Cronin. But I knew I was in one of the best places in the world to figure out and treat this rare disease.

Cronins pre-transplant care was spearheaded by oncologists David Fisher, MD, and Nicole LeBoeuf, MD, MPH, clinical director of Cutaneous Oncology at Dana-Farber, with his transplant conducted by Corey Cutler, MD, MPH, medical director of the Adult Stem Cell Transplantation Program at Dana-Farber. Initially, Cronins disease was incredibly resistant; for nearly three years, mainstay drugs including steroids, monoclonal antibodies, and enzyme blockers all failed to put his disease into remission.

Ultimately, it would take a new drug, mogamulizumab (a type of immunotherapy that directly kills T-cells involved with Sezary Syndrome) to get Cronins disease into remission.

In May 2019, Cronin was cleared to undergo an allogeneic transplant, a type of transplant that uses a donors stem cells, in this case, Cronins brother. Since his transplant Cronin has remained in remission.

We had to use all of our big guns to get him totransplant, but Im pleased with where we are now, says Cutler.

I know the situation can always change, but it was great tobe able to share some good news with my family and friends, adds Cronin.

Patients like Cronin serve as a reminder of how stem cell transplants have improved and continue to impact patient outcomes, Dana-Farber experts note. Initially offered to only an incredibly small patient population when first performed at Dana-Farber in the 1970s, research advancements have, and continue to, broaden who is eligible for a transplant. In 2019, Dana-Farber/Brigham and Womens Cancer Center (DF/BWCC) surpassed 10,000 total adult transplants.

This milestone indicates our success as a program and our volume has allowed us to do the research to help move the field forward rather impressively, says Joseph Antin, MD, chief emeritus of Adult Stem Cell Transplantation at DF/BWCC.

In 1996, Dana-Farber Cancer Institute and Brigham and Womens Hospital merged their then separate transplant centers. By pooling together physical and intellectual resources, the new combined program was able to more than double the number of transplants each hospital could perform individually.

We always felt collaboration was better than competition, explains Robert Soiffer, MD, vice chair of Medical Oncology for Hematological Malignancies and chief of the Division of Hematologic Malignancies, who oversaw the merger with Antin. Each side could learn from the other, and that helped to catapult us into the leadership position we have today.

The Stem Cell Transplantation Program is also bolstered by the Connell and OReilly Families Cell Manipulation Core Facility (CMCF), which was established in 1996. The state-of-the-art center, led by Jerome Ritz, MD, not only processes the stem cells for transplant; it also assists researchers in developing new cell-based therapies for patients.

Another key component to the programs success has been the creation of the Ted and Eileen Pasquarello Tissue Bank. The Pasquarello Tissue Bank receives, processes, banks, and distributes research samplesof blood, bone marrow, and other tissues. Through a database overseen by Vincent Ho, MD, the Institute is able to log, assess, and later review every patients disease, including all complications and mutations. This technology allows researchers to explore the genetic makeup of past donors and better understand why a transplant was or was not successful.

Were still learning from biological specimens we collected 20 years ago, and it will continue to impact care 20 years from now, Soiffer says.

Today, there is a continuous push to develop new and more precise therapies to complement and improve stem cell transplants. The hope is to bring new treatment options to patients like Cronin who are facing rare and difficult diseases.

Before his diagnosis, Bill, and Barbara Finney, his partner ofnearly 30 years, were avid English Country dancers. English Country dancingevolved from the court dances of Europe in the early 17th century, and Croninand Barbara have friends from all over the country who share their passion forit.

While Cronin isnt dancing just yet, as hes stillrecovering from his transplant, he says he couldnt have gotten through thiswithout his partner on the dance floor and in life.

Barbara has been amazing and has helped take care ofeverything I couldnt do, he adds. Ive been fortunate and privileged to notonly have her, but to have been able to come to Dana-Farber.

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Transplant for Szary Syndrome is Patient's First Step in Returning to the Dance Floor - Dana-Farber Cancer Institute

Eternal youth and good health from stem cells soon within reach? – Innovation Origins

Could one of humankinds wildest dreams eternal youth and eternal good health perhaps come true after all? Well, were probably not quite there yet. But a new discovery in stem cell research may well constitute a step in this direction. Researchers led by biologist Vlad Cojocaru from the Dutch Hubrecht Institute, together with colleagues from the Max Planck Institute in Mnster, Germany, have discovered how normal human cells can be transformed into stem cells.

Differentiation between cell types is based on whether the DNA is read or not read at a specific point in time. Here, proteins known as transcription factors send the signal to read DNA in the cell or to halt the process of reading. Identity transformations, whereby cells move from an undesignated cell type to a designated cell type, occur naturally during development. However, these transformations can also be reversed. Japanese researchers were awarded the Nobel Prize in 2012 after they succeeded for the first time in reverse engineering a normal skin cell back to a stem cell.

However, it is not yet fully understood how this transformation of a skin cell into a stem cell takes place on a molecular level. A thorough understanding of the processes involving atomic details is essential if we are to produce such cells reliably and efficiently for individual patients in the future, says research leader Vlad Cojocaru. It is assumed that these types of artificially produced cells could in future be part of a remedy for diseases such as Alzheimers and Parkinsons. But the production process would have to become more efficient and predictive.

A key role in stem cell formation is played by a protein known as Oct4. This triggers the activity of the proteins that reset the adult cell as a stem cell. These genes are located in the same structure that stores the DNA in the nucleus the chromatin and are no longer active in the adult cells. Known as a pioneer transcription factor, Oct4 contributes to the opening-up of the chromatin and hence facilitates gene expression.

The study data reveals how the binding of Oct4 to DNA on the nucleosomes works. We have modelled Oct4 in various configurations, explains Cojocaru. The molecule consists of two domains, only one of which is capable of binding to a specific DNA sequence on the nucleosome at this stage of the process. With our simulations, we have been able to find out which of these configurations are stable. And how the dynamics of the nucleosomes influences the binding of Oct4. The models have been validated by experiments carried out by our colleagues Caitlin MacCarthy and Hans Schler in Mnster.

More IO articles on stem cell research here.

It was the first time that computer simulations were able to show how a pioneer transcription factor binds to nucleosomes that opens up the chromatin and regulates gene expression. Cojocaru explains that this computational approach for acquiring Oct4 models could also be used to screen other transcription factors and find out how they bind to nucleosomes.

In the following step, Cojocaru plans to fine-tune the current Oct4 models in order to find a definitive structure for the Oct4 nucleosome complex. We have known for almost 15 years that Oct4, together with three other pioneering factors, transforms adult cells into stem cells. But we still dont know how they work. The scientist emphasizes that the experimental structure definition for such a system is extremely expensive and time-consuming. Thats why he and his colleagues hope to use computer simulations in combination with a range of laboratory experiments to get a definitive model for the binding of Oct4 to the nucleosome. We hope that our definitive model will enable us to pioneer the development of transcription factors for the efficient and reliable production of stem cells and other cells required in regenerative medicine.

Results of the study were published in the Biophysical Journal.

Title photo: The pioneer transcription factor Oct4 (blue) binds to the nucleosome {a complex of proteins (green) and the DNA wrapped around these proteins (orange)}. Jan Huertas and Vlad Cojocaru, MPI Mnster, Hubrecht Institute.

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Eternal youth and good health from stem cells soon within reach? - Innovation Origins

How do body parts grow to their right sizes? – The Week Magazine

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Living things just seem to know how big to grow and how big to grow their sundry parts. A human liver maintains itself at just the right volume to do its job. A fruit fly's wings, on opposite sides of its body, somehow wind up the same size as each other, correctly scaled to sustain flight.

In everyday life, we expect body parts to be in proportion, because they usually are. "You notice if somebody comes up in front of you and one leg is way bigger than the other," says Ben Stanger, a gastroenterologist and researcher at the University of Pennsylvania's Perelman School of Medicine, who has studied organ growth.

But as much as we take this basic aspect of life on Earth for granted, scientists don't fully understand it. How do body parts know when to start and stop growing?

In some cases, cells seem to follow an intrinsic program carried out by the activity of their genes. At other times, cells appear to react to a cacophony of messages they receive from other cells and their environment, turning growth on and off as needed.

A lot of times, they seem to do a little of both. And when they're cancer cells, the whole business has gone awry.

"We don't get it," says Stanger, author of a 2015 article in the Annual Review of Physiology that described mechanisms that control liver growth.

Starting with salamanders

Scientists have been trying to "get it" for a long time. In the 1930s, Yale zoologists Victor Twitty and Joseph Schwind conducted experiments in salamanders, cross-transplanting limb buds from a smaller species, Ambystoma punctatum, with those of a larger but closely related species, Ambystoma tigrinium. In some experiments, the researchers found that taking a limb bud from the small salamander and grafting it onto the larger salamander resulted in an animal with three large limbs and one small one (and vice versa). This suggests that "the information for size was embedded in that group of cells very early on and didn't care what was happening in the animal," Stanger says.

But Twitty and Schwind found in other experiments that nutrition an external regulator also affected limb size. "It's nature and it's nurture," Stanger says. "In biology, it's never either/or."

Developmental biologists soon discovered a variety of ways that organs and structures achieve their ultimate sizes. In one famous 1960s experiment, researcher Donald Metcalf implanted 6 or 12 fetal mouse spleens into individual adult mice whose own spleens had been removed. He found that each implanted spleen grew to a proportional fraction of the size of a normal adult spleen leaving the animal with a normal total amount of spleen material. This suggests that spleen tissue has a way of understanding how much of it there is in relation to the body, says Jamie Davies, an experimental anatomist at the University of Edinburgh in Scotland. But "really annoyingly," Davies says Metcalf also found that multiple thymus grafts implanted in an adult mouse behave completely differently: Each grows to its full adult size.

Decades later, Stanger found similar growth differences in the mouse liver and pancreas: Cells that give rise to the liver use environmental cues to determine how much the developing organ should grow, while those that form the pancreas follow an "autonomous trajectory" they always achieve a preprogrammed size, no matter what is going on around them.

Pumping the brakes on growth

Scientists have sussed out a reasonable amount of detail about some of the feedback-based programs that direct growth. A protein called myostatin, for instance, helps to suppress muscle growth. When the tissues get large enough to pump out a threshold amount, muscle cells stop growing. The molecular processes that dynamically regulate liver size seem to involve tissues in the gut: When levels of bile acid fall (a sign of reduced liver function), those gut tissues produce factors that disengage a brake on liver growth known as the Hippo pathway. As a result, growth kicks into gear allowing the liver to grow to its proper size. When bile acid levels rise to normal, Hippo comes back on, and liver growth turns off again. And so on.

The Hippo pathway is a super-popular subject of study today, both because of its job in regulating organ size and because of its potential role in controlling cancers. Many questions about it remain unanswered.

Mysteries also remain for cases where instructions for size are baked in, as seen in those early experiments with salamander limbs, says Laura Johnston, a geneticist and developmental biologist at Columbia University Medical Center. Labs are delving into a number of inputs that may play a role in directing cells to grow, from information about cell fates and cell organization that are hardwired in the DNA, to mechanical forces on tissues.

Johnston's own research, some of which she and her coauthors described in a 2009 article in the Annual Review of Cell and Developmental Biology, focuses on a phenomenon known as cell competition interactions that lead to the deaths of unfit or unneeded cells. It seems to play a role in stabilizing organ size. When researchers in her lab blocked cell-death mechanisms in the cells that give rise to fruit fly wings, they found that the bell-curve-shaped distribution of wing sizes normally seen in fly populations broke down. A larger-than-usual number of flies developed overly large wings, or overly small ones. It's as if, she says, "the precision of size regulation is lost if the cells can't do these competing interactions."

There's still much to learn out about the deceptively simple, fundamental questions of how an arm matches its corresponding limb or how a liver ends up just the needed size. But the questions have practical ramifications too. Many growth studies today, including myriad explorations of the Hippo pathway, are conducted in the service of understanding and treating cancers. "Researchers are saying, 'Look cancer is development gone wrong, and it's obviously growth-connected, so we really need to understand growth on its own,'" Davies says.

Also interested in organ growth are researchers who want to engineer tissues using stem cells. "There's always the worry that if you build something that will grow up inside the body," Davies says, "will it know when to stop?"

This article originally appeared in Knowable Magazine, an independent journalistic endeavor from Annual Reviews. Sign up for the newsletter.

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How do body parts grow to their right sizes? - The Week Magazine

8-year-old bone marrow recipient and donor celebrate in emotional reunion – WFAA.com

DALLAS It is more blessed to give than to receive. That's what a Bible verse says. And watching the smiles of a now healthy 8-year-old boy, that's what a recent bone marrow donor will gladly tell you too.

"I felt like the earth underneath my legs was pulled out and like I didn't know what to do," said Anitha Nagilla of Frisco of the 2017 chronic myeloid leukemia diagnosis for her then 6-year-old son Akshaj.

After chemotherapy and other treatments, he would need a bone marrow transplant to regenerate his immune system. But no one in his family, including his older sister, was a close enough match. Also, the likelihood of someone with Asian Indian heritage having a matched, available donor is only 41%.

The Nagilla family moved to north Texas from southern India 13 years ago.

WFAA

Every three minutes, someone is diagnosed with a blood cancer, like leukemia or lymphoma. For many patients, finding a bone marrow donor who is a match is their only chance for a cure. Finding a match can happen anywhere in the world at any time.

In nearby Colleyville, another immigrant, unknowingly, was about to help save the Akshaj's life.

WFAA

"Typical immigration story. Parents moved for a better life for their children and for themselves," said Dr. Prasanthi Ganesa, an oncologist who works at the Center for Cancer and Blood disorders in Fort Worth.

Dr. Ganesa moved to the U.S. as a 10-year-old child, also from southern India. She now works with adult cancer patients.

But as a medical student at Texas A&M, she and a group of friends decided to join the nationalBone Marrow Registry. The donation of blood, stem cells, and bone marrow can help people recover from a variety of cancer-related illnesses.

"At that time it was pretty simple," Dr. Ganesa said of joining the registry approximately 17 years ago. "You fill out some paperwork. It's a (saliva) swab and they have my information. So I've been on it, really not thinking about it, until I got the call. It was a surprise. It was a delightful surprise."

The surprise was that she was a match for a young boy, the same age as her own youngest child. After an outpatient procedure where marrow was extracted from a location on each hip, she went home, then back to work, and waited to hear what happened to whoever it was that received her donation.

Dr. Prasanthi Ganesa

Friday morning at Children's Medical Center in Dallas, she met him face to face.

In a meeting room all decorated for Valentine's Day, they celebrated what is also known as "National Donor Day."

"Hi buddy, how are you?" Dr. Ganesa said as she reached out to hug 8-year-old Akshaj Nagilla. "Oh my goodness," she said as they embraced.

"Definitely is on the list of one of my happiest proudest moments in my life," Dr. Ganesa said. "And Akshaj I have you to thank for that. You know what this means right? We're gonna have to be friends forever," she said as the audience of doctors, nurses, and family and friends laughed and applauded.

Being on the marrow registry is easy. All it takes is a swab of saliva. And minority donors are needed the most. Dr. Ganesa was one of two marrow donors for Akshaj. She supplied the first donation.

Akshaj initially recovered but relapsed in the fall of 2018, when he received a second transplant from a different donor, also of Asian Indian heritage. But his family credits the first donation with starting his long road to recovery.

"She being close here in Dallas is undoubtedly remarkable, in that it happened to our family," Anitha Nagilla said.

"She saved my son's life directly. But she saved some other lives as well in the family," Nagilla said of the impact on her entire extended family. "She is a lifesaver for others as well."

Friday morning at their first meeting, the Nagilla family presented Dr. Ganesa with a gold bracelet and a card with a personal message from Akshaj inside. "I'm doing good and wish you well always", he wrote.

"How wonderful is this," Dr. Ganesa said as they embraced again.

The usually shy 8-year-old also mustered up the courage to climb up to a podium and address the entire crowd, but mostly his message was for Dr. Ganesa.

"I am very thankful because I am still alive," he said.

"I just encourage everybody of Indian origin, of southeast Asian origin, any minority group to get yourself on the registry because it could save a life," Dr. Ganesa said.

"It feels really good to be able to say I gave a part of myself and I saved this person's life. I think it's the ultimate meaning of being a human being. We are here to love all serve all. And what an opportunity that I have had. So I am so grateful that I've had that opportunity," Dr. Ganesa said.

She says she feels like she received more than she gave. As she, her own two sons and the Nagilla family gathered for a group hug, her own extended family maybe just got a lot bigger too.

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8-year-old bone marrow recipient and donor celebrate in emotional reunion - WFAA.com

Singapore researchers discover Human Stem Cells and Cancer Origins in Stomach – BSA bureau

A newly identified genetic marker Aquaporin-5 (AQP5) was key to the landmark finding

An international team has, for the first time, identified and isolated human stomach stem cells that are responsible for renewing stomach tissues. They further proved that healthy stomach stem cells, after mutation, are a major source of stomach cancer. A newly identified genetic marker Aquaporin-5 (AQP5) was key to the landmark finding, which points the way to new therapeutic opportunities in future, including the development of regenerative medicine and improved stomach cancer treatments.

Stomach cancer, also known as gastric cancer, is the fifth most common cancer worldwide and the third deadliest. The high incidence rates in Asia have highlighted an unmet need to study the role of stem cells in tissue maintenance and cancer of the stomach.

The nine-year long research project was led by Agency for Science, Technology and Researchs (A*STAR) Institute of Medical Biology (IMB), in collaboration with Genome Institute of Singapore (GIS), National University Singapore (NUS), National University Health System (NUHS), Cancer Research Institute of Kanazawa University, Japan, and Maastricht University, Netherlands; its findings were published inNaturejournal on 5 February 2020.

The study built on IMBs earlier findings of Lgr5-expressing stem cells at the gland base of the mouse stomach. Adult stem cells, marked by the Lgr5 protein, are responsible for the continuous regeneration and replacement of tissues in many organs, but can also cause cancer if damaged. Although Lgr5 is a selective marker of stomach stem cells in the mouse, researchers could not previously identify the equivalent Lgr5-expressing stem cells from human tissues due to the lack of surface markers that enable its isolation and validation. Furthermore, as Lgr5 is expressed across a diverse range of tissues including the intestine, stomach and kidney, the team was unable to target cancer-causing mutations specific to the stomach stem cells to evaluate their role in stomach cancer.

Using the Lgr5 marker, the team found AQP5, a new surface marker that allowed them to isolate human stomach stem cells using antibodies, and functionally proved that they were stem cells. Using the new AQP5 marker to selectively introduce mutations to the stomach stem cells in mice, the researchers were able to highlight their role in driving the early formation of Wnt-driven gastric cancer. Importantly, they subsequently showed that stomach tumours harbour populations of AQP5-expressing cells that could behave as cancer stem cells to drive cancer growth. These important findings deliver crucial insights into gastric cancer progression and reveal key therapeutic targets for prospective development as more effective stomach cancer treatments in the clinic. The ability to isolate human stem cells for the first time also offers great potential for harnessing their regenerative medicine potential in clinical settings.

Using a new method to evaluate the frequency with which key signaling pathways display altered behavior in human cancer samples, the study further revealed that the hyperactivated Wnt pathway is much more prevalent in gastric cancer than previously thought. This highlights the therapeutic potential of drugs targeting the Wnt pathway for treating a wide range of human gastric cancers.

Professor Nick Barker, Research Director at A*STAR IMB said, Our work facilitates for the first time, the isolation of mouse and human stomach stem cells using antibodies, identifies dysregulation of the Wnt pathway as a frequent event in human cancer, and reveals stomach stem cells as important sources of gastric cancer. Our ability to identify and purify tumour-resident stem cells in gastric cancer using the new AQP5 marker will allow us to directly evaluate their role in human cancer formation, characterise them in depth and potentially develop drug-screening tests to identify ways to selectively kill these cells.

It takes time and resources to bring well-grounded basic research to fruition and translate them into benefits for society. Findings from our study should help to clarify the identity and role of stomach cells in cancer and we hope that they can be translated to positive clinical outcomes in the future.

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Singapore researchers discover Human Stem Cells and Cancer Origins in Stomach - BSA bureau

Stem Cell And Regenerative Therapy Market Sales Volume, Status, Growth, Opportunities and World – Instant Tech News

The global stem cell and regenerative medicines market should grow from $21.8 billion in 2019 to reach $55.0 billion by 2024 at a compound annual growth rate (CAGR) of 20.4% for the period of 2019-2024.

Report Scope:

The scope of this report is broad and covers various type of product available in the stem cell and regenerative medicines market and potential application sectors across various industries. The current report offers a detailed analysis of the stem cell and regenerative medicines market.

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The report highlights the current and future market potential of stem cell and regenerative medicines and provides a detailed analysis of the competitive environment, recent development, merger and acquisition, drivers, restraints, and technology background in the market. The report also covers market projections through 2024.

The report details market shares of stem cell and regenerative medicines based on products, application, and geography. Based on product the market is segmented into therapeutic products, cell banking, tools and reagents. The therapeutics products segments include cell therapy, tissue engineering and gene therapy. By application, the market is segmented into oncology, cardiovascular disorders, dermatology, orthopedic applications, central nervous system disorders, diabetes, others

The market is segmented by geography into the following regions: North America, Europe, Asia-Pacific, South America, and the Middle East and Africa. The report presents detailed analyses of major countries such as the U.S., Canada, Mexico, Germany, the U.K. France, Japan, China and India. For market estimates, data is provided for 2018 as the base year, with forecasts for 2019 through 2024. Estimated values are based on product manufacturers total revenues. Projected and forecasted revenue values are in constant U.S. dollars, unadjusted for inflation.

Report Includes:

28 data tables An overview of global markets for stem cell and regenerative medicines Analyses of global market trends, with data from 2018, estimates for 2019, and projections of compound annual growth rates (CAGRs) through 2024 Details of historic background and description of embryonic and adult stem cells Information on stem cell banking and stem cell research A look at the growing research & development activities in regenerative medicine Coverage of ethical issues in stem cell research & regulatory constraints on biopharmaceuticals Comprehensive company profiles of key players in the market, including Aldagen Inc., Caladrius Biosciences Inc., Daiichi Sankyo Co. Ltd., Gamida Cell Ltd. and Novartis AG

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Summary

The global market for stem cell and regenerative medicines was valued at REDACTED billion in 2018. The market is expected to grow at a compound annual growth rate (CAGR) of REDACTED to reach approximately REDACTED billion by 2024. Growth of the global market is attributed to the factors such as growingprevalence of cancer, technological advancement in product, growing adoption of novel therapeuticssuch as cell therapy, gene therapy in treatment of chronic diseases and increasing investment fromprivate players in cell-based therapies.

In the global market, North America held the highest market share in 2018. The Asia-Pacific region is anticipated to grow at the highest CAGR during the forecast period. The growing government funding for regenerative medicines in research institutes along with the growing number of clinical trials based on cell-based therapy and investment in R&D activities is expected to supplement the growth of the stem cell and regenerative market in Asia-Pacific region during the forecast period.

Reasons for Doing This Study

Global stem cell and regenerative medicines market comprises of various products for novel therapeutics that are adopted across various applications. New advancement and product launches have influenced the stem cell and regenerative medicines market and it is expected to grow in the near future. The biopharmaceutical companies are investing significantly in cell-based therapeutics. The government organizations are funding research and development activities related to stem cell research. These factors are impacting the stem cell and regenerative medicines market positively and augmenting the demand of stem cell and regenerative therapy among different application segments. The market is impacted through adoption of stem cell therapy. The key players in the market are investing in development of innovative products. The stem cell therapy market is likely to grow during the forecast period owing to growing investment from private companies, increasing in regulatory approval of stem cell-based therapeutics for treatment of chronic diseases and growth in commercial applications of regenerative medicine.

Products based on stem cells do not yet form an established market, but unlike some other potential applications of bioscience, stem cell technology has already produced many significant products in important therapeutic areas. The potential scope of the stem cell market is now becoming clear, and it is appropriate to review the technology, see its current practical applications, evaluate the participating companies and look to its future.

The report provides the reader with a background on stem cell and regenerative therapy, analyzes the current factors influencing the market, provides decision-makers the tools that inform decisions about expansion and penetration in this market.

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Stem Cell And Regenerative Therapy Market Sales Volume, Status, Growth, Opportunities and World - Instant Tech News