Category Archives: Stem Cells

Apr 10, 2015 by Stephanie Dutchen New research indicates how and when adult intestinal stem cells (dark pink) set up shop at the base of villi, as shown in this image from the intestine of a chick near hatching. Credit: Tabin lab

Mommy, where do intestinal stem cells come from? All right, it's not likely a kindergartner would ask such a question. But evolutionary biologists want to know.

Adult intestinal stem cells live at the bases of our villi, the tiny, fingerlike protuberances that line the intestines and absorb nutrients.

There, the stem cells constantly churn out new intestinal cells to replace those being destroyed by corrosive digestive juices.

The researchers asked: How and when do these stem cells appear in the right place so they can do their job?

Studying mice and chicks, whose intestinal formation is similar to ours, the team found that the entire intestinal lining has stem cell properties at first. As the embryo develops, all but a few cells lose this potential.

"This lends support to the theory that adult stem cells are remnants of a more general pool of cells in the embryo," said Amy Shyer, who conducted the work as a graduate student in the lab of Cliff Tabin at Harvard Medical School and is now a Miller Fellow at the University of California, Berkeley.

As for why these cells are restricted to the villi bases, or crypts, the researchers believe the structure of the developing intestine determines which cells receive signals from neighboring tissues that say, "Stop being stem cells."

About two weeks into development, the intestine, initially a smooth tube, starts to form mountainous zigzags that will ultimately become villi. Cells at the peaks are exposed to signals that suppress stem cell properties, while cells in the valleys don't receive them.

"This opens a new door conceptually," said Shyer. "Tissues that start out uniform but then need to set up regions with regular patternswhich happens in the gut, skin, lungs and other organs during embryonic developmentmight coopt these natural changes in architecture to dictate signals that specify cell fate locally."

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Gut instinct: How intestinal stem cells find their niche

Rice University and Texas Children's Hospital scientists are using stem cells from amniotic fluid to promote the growth of robust, functional blood vessels in healing hydrogels.

In new experiments, the lab of bioengineer Jeffrey Jacot combined versatile amniotic stem cells with injectable hydrogels used as scaffolds in regenerative medicine and proved they enhance the development of vessels needed to bring blood to new tissue and carry waste products away.

The results appear in the Journal of Biomedical Materials Research Part A.

Jacot and his colleagues study the use of amniotic fluid cells from pregnant women to help heal infants born with congenital heart defects. Such fluids, drawn during standard tests, are generally discarded but show promise for implants made from a baby's own genetically matched material.

He contends amniotic stem cells are valuable for their ability to differentiate into many other types of cells, including endothelial cells that form blood vessels.

"The main thing we've figured out is how to get a vascularized device: laboratory-grown tissue that is made entirely from amniotic fluid cells," Jacot said. "We showed it's possible to use only cells derived from amniotic fluid."

In the lab, researchers from Rice, Texas Children's Hospital and Baylor College of Medicine combined amniotic fluid stem cells with a hydrogel made from polyethylene glycol and fibrin. Fibrin is a biopolymer critical to blood clotting, cellular-matrix interactions, wound healing and angiogenesis, the process by which new vessels branch off from existing ones. Fibrin is widely used as a bioscaffold but suffers from low mechanical stiffness and rapid degradation. Combining fibrin and polyethylene glycol made the hydrogel much more robust, Jacot said.

The lab used vascular endothelial growth factor to prompt stem cells to turn into endothelial cells, while the presence of fibrin encouraged the infiltration of native vasculature from neighboring tissue.

Mice injected with fibrin-only hydrogels showed the development of thin fibril structures, while those infused with the amniotic cell/fibrin hydrogel showed far more robust vasculature, according to the researchers.

Similar experiments using hydrogel seeded with bone marrow-derived mesenchymal cells also showed vascular growth, but without the guarantee of a tissue match, Jacot said. Seeding with endothelial cells didn't work as well as the researchers expected, he said.

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Amniotic stem cells demonstrate healing potential

SALT LAKE CITY, Utah -

Rachel Taylor was diagnosed with multiple sclerosis 14 years ago.

"It was terrifying. It was like having a wet, heavy blanket put over your life. I was active. I was a runner. I was outdoors playing, and over the course of a few months, I couldn't figure out why I couldn't keep up" Taylor recalled.

Taylor knew what was wrong. She'd been working with the MS Society bike rides for years.

Taylor is in remission now, but she is still thrilled with Tom Lane, professor of pathology at the University of Utahs stem cell discovery.

"We have animals that are paralyzed that cannot right themselves, and once we engraft the neural stem cells into the spinal cords, within three weeks, the majority of the animals, about 80 to 85 percent, will regain motor skills," Lane said.

Researchers said MS damages myelin, a layer around nerve cells. Once injected, the human neural cells stimulate the mouse's own cells to repair the damage. When nerve cell function returns, the mice can walk and run again.

Taylor said the discovery could be life-changing for many of her friends. Researchers said after the mice regained function, their bodies rejected the stem cells, which vanished, eliminating the possibility that those cells could become tumors.

Lane is hoping this procedure could be ready for human clinical trials in two to three years.

DOWNLOAD and VIEW research summary and an in-depth interview with the doctor

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Health Beat: Stem cells reverse multiple sclerosis

Miami, FL (PRWEB) April 09, 2015

Global Stem Cells Group subsidiary Adimarket has been named the Latin America distributor for bone marrow technology leader Ranfac Corporation. The announcement coincides with Global Stem Cells Groups most recent expansion plans in Latin America, an ongoing effort to meet the regions growing demands for access to regenerative medicine and stem cell therapies.

Ranfac manufactures state-of-the-art surgical, radiology, hematology and orthopedic products including a range of bone marrow aspiration needles, each designed to provide a simple means of harvesting marrow from the patients sternum (breastbone) or the iliac crest (part of the pelvic bone) for a variety of medical procedures. Ranfacs newest technology is designed to harvest high quality bone marrow derived cells without the need for centrifugation.

Ranfac bone marrow technology is used by physicians and medical specialists worldwide. Global Stem Cells Group Advisory Board member Joseph Purita, M.D., a pioneer in the use of laser and stem cell therapies in orthopedic medicine, endorses Ranfacs bone marrow aspiration technology. Purita recently joined other specialists including fellow GSCG Advisory Board member David B Harrell, PhD, Brt, OF, FAARM, FRIPH, DABRM, in a trial study and white paper collaboration on Ranfacs new, non-centrifugal bone marrow technology.

Both Purita and Harrell endorse the Ranfac systems enhanced safety and ability to increase the concentrations of stem and progenitor cells during the bone marrow aspiration process.

Our ground-breaking hematology and orthopedic products for bone marrow access, aspiration, stem cell harvesting and biopsy procedures are designed to provide a more efficient result during critical procedures, says Ranfac CEO Barry Zimble. We believe that this is the perfect time to team with Global Stem Cells Group as our distribution partner in Latin Americas fast-growing medical community.

The collaboration between Global Stem Cells Group and Ranfac is another step toward GSCGs commitment to expanding its presence in communities that need and deserve access to cutting-edge regenerative medicine, not only in Latin America but also worldwide.

The timing couldnt be better to represent Ranfacs cutting edge bone marrow technology in the emerging markets of Latin America. Global is always looking to provide patients and practitioners with the best resources that regenerative medicine has to offer says Ricardo DeCubas, Global Stem Cells Group co-founder and Regenestem CEO.

For more information visit the Global Stem Cells Group website, email bnovas@stemcellsgroup.com, or call 305-224-1858.

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Global Stem Cells Group Subsidiary Adimarket Named Latin American Distributor for Ranfac Bone Marrow Technology

PRESS RELEASE

USPTO issues key US patent to TiGenix for the use of adipose-derived stromal cells in the treatment of fistulas

Leuven (BELGIUM) - 8 April, 2015 -TiGenix NV (Euronext Brussels: TIG), an advanced biopharmaceutical company focused on developing and commercialising novel therapeutics from its proprietary platform of allogeneic expanded adipose-derived stem cells in inflammatory and autoimmune diseases, announced today that the United States Patent and Trademark Office (USPTO) has issued US Patent 8,999,709 relating to the use of an adipose-derived stromal cell population in the treatment of fistula. The patent, entitled "Use of adipose tissue-derived stromal stem cells in treating fistula", expires in 2030 and provides coverage for the company's lead development product, Cx601, in the key US market.

"The issuance by the USPTO of this patent is a key achievement in our strategy for the development and commercialisation of Cx601 in the American market", said Wilfried Dalemans, Chief Technical Officer of TiGenix. "It further builds our intellectual property position in the use of eASCs in the indication we are pursuing. As such, it is an essential component of the business case for making the product available to patients in the US."

The issuance of this patent further strengthens TiGenix's intellectual property portfolio of 24 patent families which now includes 15 granted patents related specifically to its eASC platform. The pending and granted patents in TiGenix's intellectual property portfolio include patent families that are directed to its eASC platform; more specifically, to eASC compositions and therapeutic applications as well as to cell therapy delivery mechanisms and other eASC technology improvements.

Cx601 is a solution of expanded adipose-derived stem cells (eASCs) for local injection currently in Phase III of clinical development for the treatment of complex perianal fistulas in patients with Crohn's disease. Clinical results from the on-going European Phase III trial are expected in the third quarter of 2015. Following the positive feedback received at a meeting with the Center for Biologics Evaluation and Research within the Food and Drug Administration (FDA), TiGenix is moving ahead with the development of Cx601 for the United States market. The Company has submitted to the FDA the required documentation for a Special Protocol Assessment (SPA) of its pivotal Phase III trial design for Cx601 in the treatment of complex perianal fistulas in patients with Crohn's disease in the United States. Agreement with the FDA on the SPA will ensure that the trial design is aligned with the FDA's requirements for the future approval of Cx601. The Phase III trial in the US, if successful, together with positive data from the European Phase III trial, would enable the Company to file a biologics license application (BLA) with the FDA. The Company expects to complete the process of manufacturing technology transfer to its US-based contract manufacturing organisation (CMO), Lonza, in the first half of 2016, after which the Phase III trial of Cx601 in the US can begin.

For more information:

Richard Simpson Senior Consultant, Comfi sprl T: +32 494 578 278 richard@comfi.be

About Cx601

Cx601 is a suspension of allogeneic expanded adipose-derived stem cells (eASCs) delivered locally through intra-lesional injection. Cx601 is being developed for the treatment of perianal fistulas in Crohn's disease patients. Crohn's disease is a chronic inflammatory disease of the intestine and patients can suffer from complex perianal fistulas for which there is currently no effective treatment. In 2009, the European Commission granted Cx601 orphan designation for the treatment of anal fistulas, recognising the debilitating nature of the disease and the lack of treatment options. In a Phase II clinical trial, Cx601 showed efficacy at 24 weeks in 56% of treated fistula tracts, which is more than two times higher than the current standard of care (TNF inhibitors). Efficacy was measured as the complete closure and re-epithelisation of the fistula being treated with an absence of drainage. Additionally, 69.2% of patients demonstrated a reduction in the number of initially draining tracts. The trial also confirmed the safety of the use of allogeneic stem cells for the treatment of perianal fistula. Based on these results, TiGenix sought scientific advice from the European Medicines Agency (EMA) on the future development path of Cx601. TiGenix then initiated a randomised, double-blind, placebo-controlled Phase III trial in Europe and Israel designed to comply with the requirements laid down by the EMA. 'Madrid Network', an organisation within the Autonomous Region of Madrid which helps companies to grow through high-technology innovation, issued a soft loan to help finance this Phase III study. The programme is funded by The Secretary of State for Research, Development and Innovation (Ministry of Economy and Competitiveness) within the framework of the INNTEGRA plan. This pivotal study is intended to enable filing for marketing authorisation in Europe and to serve as a key supportive study in filing for approval in other territories, including the US. The study's primary endpoint is closure of all treated external openings draining at baseline despite gentle finger compression confirmed by MRI (no collections > 2cm). The trial has a first complete analysis of results at 24 weeks, with a follow-up analysis to be performed at 52 weeks post-treatment. Recruitment of the whole sample of patients was completed in the fourth quarter of 2014. The first clinical report is expected to be available in the third quarter of 2015. With positive results, TiGenix intends to submit a request for marketing authorisation with the EMA early in 2016. TiGenix is preparing to develop Cx601 for the US market. The company has filed for a Special Protocol Assessment (SPA) by the Food and Drug Administration (FDA) to ensure that the design of a new Phase III study to be conducted in the US is aligned with the FDA's requirements for the future approval of Cx601. The company has appointed Lonza as its contract manufacturing organisation (CMO) for the clinical development of Cx601 in the US.

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TiGenix: USPTO issues key US patent to TiGenix for the use of adipose-derived stromal cells in the treatment of fistulas

Inside the microscopic world of the mouse hair follicle, Yale Cancer Center researchers have discovered big clues about how stem cells regenerate and die. These findings, reported in the journal Nature, could lead to a better understanding of how the stem cell pool is maintained or altered in tissues throughout the body.

Stem cells are undifferentiated cells that replenish themselves and based on their tissue location can become specialized cells such as blood or skin cells. The hair follicle is an ideal site for exploring stem cell behavior because it has distinct and predictable oscillations in the number and behavior of stem cells, said the study's lead author Kailin R. Mesa, a third-year doctoral student in the lab of Valentina Greco, associate professor of genetics, cell biology and dermatology.

Using live microscopic imaging to track stem cell behavior in the skin of living mice, researchers observed that the stem cell niche, or surrounding area, played a critical role in whether stem cells grow or die.

"Prior to this, it wasn't clear whether stem cell regulation was intrinsic or extrinsic, and now we know it is external in that the niche instructs the stem cells," Mesa said. "In terms of cancer, we can next explore how we might perturb or change the niche in hopes of affecting the growth of cancer stem cells."

Also, researchers were surprised to find that the stem cells within the pool fed on other dying stem cells. This reveals a mechanism for removing dead cells, a process previously observed in mammary glands but never in the skin.

Story Source:

The above story is based on materials provided by Yale Cancer Center. Note: Materials may be edited for content and length.

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Tiny hair follicle holds big clues about the life and death of stem cells

H. Lee Moffitt Cancer Center & Research Institute

TAMPA, Fla. - Lung cancer is the second most common type of cancer and the number one cause of cancer-related mortality. It is estimated that more than 158,000 people will die from lung cancer in the United States this year. Many scientists believe that targeting a type of cell called a cancer stem cell may be necessary to completely cure lung cancer. Moffitt Cancer Center researchers discovered a novel mechanism that plays an important role in the maintenance of lung cancer stem cells. This finding may lead to new potential therapeutic targets.

Cancer stem cells are a subset of cells within tumors that are believed to be responsible for the initiation of cancer. Cancer stem cells can reproduce themselves through a process called self-renewal and sustain the growth of a tumor. According to Srikumar P. Chellappan, Ph.D., chair of the Department of Tumor Biology at Moffitt, "these cells can also contribute to the metastasis of tumors as well as the reappearance of tumors after they have been eliminated from the body."

A protein called YAP1 was previously shown to contribute to the growth of lung cancer cells; however, it was unknown how YAP1 controls lung cancer growth and progression. Moffitt researchers found that YAP1 plays an important role in cancer stem cell self-renewal.

They reported that YAP1 is found at high levels in lung cancer stem cells and binds to a protein called OCT4. Together, YAP1 and OCT4 regulate a third protein called SOX2. This intricate regulation process allows stem cells to maintain their ability to undergo self-renewal and form blood vessel-like structures.

The team compared the levels of YAP1 and OCT4 in lung cancer and normal tissue. They discovered that YAP1 is present at higher levels and interacts with OCT4 more in primary and metastatic lung tumors than normal tissue. Additionally, lung cancer patients who have high levels of YAP1 in their tumors are more likely to have a poorer prognosis than patients with low levels of YAP1. These observations suggest that YAP1 may be a potential therapeutic target.

The researchers confirmed this hypothesis by showing that if they blocked YAP1 they could inhibit stem cells from undergoing self-renewal, forming blood vessel-like structures, and reduce lung cancer cell growth in mice.

"These results raise the possibility that inhibitors of YAP1 function or agents that can disrupt the binding of YAP1 to OCT4 could have anti-cancer effects. The identification of novel and effective inhibitors of YAP1 activity can be expected to have significant benefits as anticancer agents," explained Chellappan.

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This study was published in the March 6 edition of the journal Stem Cells, and was supported by grants from the National Institutes of Health (CA127725 and CA139612).

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Moffitt researchers discover novel mechanism controlling lung cancer stem cell growth

14 hours ago by Vicky Agnew

Inside the microscopic world of the mouse hair follicle, Yale Cancer Center researchers have discovered big clues about how stem cells regenerate and die. These findings, published April 6 in the journal Nature, could lead to a better understanding of how the stem cell pool is maintained or altered in tissues throughout the body.

Stem cells are undifferentiated cells that replenish themselves and, based on their tissue location, can become specialized cells such as blood or skin cells. The hair follicle is an ideal site for exploring stem cell behavior because it has distinct and predictable oscillations in the number and behavior of stem cells, said the study's lead author, Kailin R. Mesa, a third-year doctoral student in the lab of Valentina Greco, associate professor of genetics, cell biology, and dermatology.

Using live microscopic imaging to track stem cell behavior in the skin of living mice, researchers observed that the stem cell niche, or surrounding area, plays a critical role in whether stem cells grow or die.

"Prior to this, it wasn't clear whether stem cell regulation was intrinsic or extrinsic, and now we know it is external in that the niche instructs the stem cells," Mesa said. "In terms of cancer, we can next explore how we might perturb or change the niche in hopes of affecting the growth of cancer stem cells."

Also, researchers were surprised to find that the stem cells within the pool fed on other dying stem cells. This reveals a mechanism for removing dead cells, a process previously observed in mammary glands but never in the skin.

Explore further: Limited self-renewal of stem cells in the brain

More information: Niche-induced cell death and epithelial phagocytosis regulate hair follicle stem cell pool, Nature, DOI: 10.1038/nature14306

Journal reference: Nature

Provided by Yale University

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Tiny hair follicle offers big clues about the life and death of stem cells

HOUSTON -

It's a debate that puts many people's religious beliefs at odds with science.

Medical breakthroughs have allowed doctors to use human stem cells to treat chronic diseases with incredible results, but even patients who benefit have reservations about how stem cells are harvested.

Multiple sclerosis is a debilitating, progressive disease that typically only gets worse once a patient is diagnosed. But much to the surprise of many doctors, patient Debbie Bertrand's symptoms have improved instead of regressing.

"The last time I walked into this building, I had to use the wheelchair," Bertrand said. "I couldn't even walk, so this is a big day for me."

Bertrand uses a walker to visit Celltex -- a Houston company that has been preserving her stem cells since 2011. She was one of the first patients to receive breakthrough treatments using stem cells taken from fat cells, which are then reinjected into her body.

"I had pretty high expectations, but I think they've exceeded anything I could've ever hoped for," Bertrand said. "My doctors are still blown away because you're never supposed to get better when you have MS. But my quality of life is just so much better."

Bertrand's experience is not unique. The company said stem cell injections have helped people with joint diseases and Parkinson's.

CEO David Eller said he was healed of knee pain.

"We're happy that it's working and we're happy for people like Debbie Bertrand," Eller said. "A lot of people don't have the time to wait 10 years and find out if it's going to be legal or not."

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Stem cell research benefits Houston woman with multiple sclerosis

HOUSTON -

It's a debate that puts many people's religious beliefs at odds with science.

Medical breakthroughs have allowed doctors to use human stem cells to treat chronic diseases with incredible results. But even patients who benefit have reservations about how stem cells are harvested.

Multiple sclerosis is a debilitating, progressive disease that typically only gets worse once a patient is diagnosed. But much to the surprise of many doctors, patient Debbie Bertrand's symptoms have improved instead of regressing.

"The last time I walked into this building, I had to use the wheelchair," Bertrand said. "I couldn't even walk, so this is a big day for me."

Bertrand uses a walker to visit Celltex -- a Houston company that has been preserving her stem cells since 2011. She was one of the first patients to receive breakthrough treatments using stem cells taken from fat cells, which are then reinjected into her body.

"I had pretty high expectations, but I think they've exceeded anything I could've ever hoped for," Bertrand said. "My doctors are still blown away because you're never supposed to get better when you have MS. But my quality of life is just so much better."

Bertrand's experience is not unique. The company said stem cell injections have helped people with joint diseases and Parkinson's.

CEO David Eller said he was healed of knee pain.

"We're happy that it's working and we're happy for people like Debbie Bertrand," Eller said. "A lot of people don't have the time to wait 10 years and find out if it's going to be legal or not."

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Stem cell research benefits area woman with multiple sclerosis