Category Archives: Stem Cells

LOS ANGELES (EMBARGOED UNTIL 7 A.M. EDT on APRIL 14, 2015) - An injection of stem cells into the eye may soon slow or reverse the effects of early-stage age-related macular degeneration, according to new research from scientists at Cedars-Sinai. Currently, there is no treatment that slows the progression of the disease, which is the leading cause of vision loss in people over 65.

"This is the first study to show preservation of vision after a single injection of adult-derived human cells into a rat model with age-related macular degeneration," said Shaomei Wang, MD, PhD, lead author of the study published in the journal STEM CELLS and a research scientist in the Eye Program at the Cedars-Sinai Board of Governors Regenerative Medicine Institute.

The stem cell injection resulted in 130 days of preserved vision in laboratory rats, which roughly equates to 16 years in humans.

Age-related macular degeneration affects upward of 15 million Americans. It occurs when the small central portion of the retina, known as the macula, deteriorates. The retina is the light-sensing nerve tissue at the back of the eye. Macular degeneration may also be caused by environmental factors, aging and a genetic predisposition.

When animal models with macular degeneration were injected with induced neural progenitor stem cells, which derive from the more commonly known induced pluripotent stem cells, healthy cells began to migrate around the retina and formed a protective layer. This protective layer prevented ongoing degeneration of the vital retinal cells responsible for vision.

Cedars-Sinai researchers in the Induced Pluripotent Stem Cell (iPSC) Core, directed by Dhruv Sareen, PhD, with support from the David and Janet Polak Foundation Stem Cell Core Laboratory, first converted adult human skin cells into powerful induced pluripotent stem cells (iPSC), which can be expanded indefinitely and then made into any cell of the human body. In this study, these induced pluripotent stem cells were then directed toward a neural progenitor cell fate, known as induced neural progenitor stem cells, or iNPCs.

"These induced neural progenitor stem cells are a novel source of adult-derived cells which should have powerful effects on slowing down vision loss associated with macular degeneration," said Clive Svendsen, PhD, director of the Board of Governors Regenerative Medicine Institute and contributing author to the study. "Though additional pre-clinical data is needed, our institute is close to a time when we can offer adult stem cells as a promising source for personalized therapies for this and other human diseases."

Next steps include testing the efficacy and safety of the stem cell injection in preclinical animal studies to provide information for applying for an investigational new drug. From there, clinical trials will be designed to test potential benefit in patients with later-stage age-related macular degeneration.

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Additional Cedars-Sinai authors include Dhruv Sareen, PhD; Yuchun Tsai, PhD; Bin Lu, MD, PhD; Benjamin Bakondi, PhD; Sergey Girman, PhD; and Anais Sahabian, PhD.

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Stem cell injection may soon reverse vision loss due to age-related macular degeneration

ANN ARBOR--Research led by the University of Michigan Life Sciences Institute has identified a gene critical to controlling the body's ability to create blood cells and immune cells from blood-forming stem cells--known as hematopoietic stem cells.

The findings, scheduled for online publication in the Journal of Clinical Investigation April 13, provide new insights into the underlying mechanics of how the body creates and maintains a healthy blood supply and immune system, both in normal conditions and in situations of stress--like the body experiences following a bone marrow transplant.

Along with helping scientists better understand the body's basic processes, the discovery opens new lines of inquiry about the Ash1l gene's potential role in cancers known to involve other members of the same gene family, like leukemia, or those where Ash1l might be highly expressed or mutated.

"It's vital to understand how the basic, underlying mechanisms function in a healthy individual if we want to try to develop interventions for when things go wrong," said study senior author Ivan Maillard, an associate research professor at the Life Sciences Institute, where his lab is located, and an associate professor in the Division of Hematology-Oncology at the U-M Medical School.

"Leukemia is a cancer of the body's blood-forming tissues, so it's an obvious place that we plan to look at next. If we find that Ash1l plays a role, then that would open up avenues to try to block or slow down its activity pharmacologically," he said.

Graduate students Morgan Jones and Jennifer Chase were the study's first authors.

Dysfunction of blood-forming stem cells is well known in illnesses like leukemia and bone marrow failure disorders. Blood-forming stem cells can also be destroyed by high doses of chemotherapy and radiation used to treat cancer. The replacement of these cells through bone marrow transplantation is the only widely established therapy involving stem cells in human patients.

But even in the absence of disease, blood cells require constant replacement--most blood cells last anywhere from a few days to a few months, depending on their type.

Over more than five years, Maillard and his collaborators identified a previously unknown but fundamental role played by the Ash1l gene in regulating the maintenance and self-renewal potential of these hematopoietic stem cells.

The Ash1l (Absent, small or homeotic 1-like) gene is part of a family of genes that includes MLL1 (Mixed Lineage Leukemia 1), a gene that is frequently mutated in patients who develop leukemia. The research found that both genes contribute to blood renewal; mild defects were seen in mice missing one or the other, but lacking both led to catastrophic deficiencies.

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U-M researchers find new gene involved in blood-forming stem cells

New $6.4M federal grant support will fuel the development of 'guts in a dish' to study interaction between cells & microbes in both health and disease

IMAGE:These HIO structures, each about the size of a BB and grown from stem cells, allow scientists to study the interaction between the cells of the gut lining and microbes... view more

Credit: University of Michigan Medical School

ANN ARBOR, Mich. -- If you got hit with any of the 'intestinal bugs' that went around this winter, you've felt the effects of infectious microbes on your digestive system.

But scientists don't fully understand what's going on in gut infections like that - or in far more serious ones that can kill. Many mysteries remain in the complex interaction between our own cells, the helpful bacteria that live inside us, and tiny invaders.

Now, a team of University of Michigan scientists will tackle that issue in a new way. Using human stem cells, they'll grow tiny "guts in a dish" in the laboratory and study how disease-causing bacteria and viruses affect the microbial ecosystem in our guts. The approach could lead to new treatments, and aid research on a wide range of diseases.

This work was started as part of the U-M Medical School's self-funded Host Microbiome Initiative and Center for Organogenesis, and the U-M Center for Gastrointestinal Research, funded by the National Institutes of Health. It also received funding from the U-M's MCubed initiative for interdisciplinary work.

Now, the project has received a $6.4 million boost with a new five-year NIH grant.

It will allow the U-M team to expand their effort to grow human intestinal organoids, or HIOs - tiny hollow spheres of cells into which they can inject a mix of bacteria. They'll work with researchers at other institutions, as part of the Novel, Alternative Model Systems for Enteric Diseases, or NAMSED, initiative sponsored by the NIH's National Institute of Allergy and Infectious Diseases.

Balls of cells become mini-guts

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To fight nasty digestive bugs, scientists set out to build a better gut -- using stem cells

Mesenchymal stem cells captured in microcapsules. Each microcapsule is roughly 40 micrometers across.

A team of Cornell scientists has shown that stem cells confined inside tiny capsules secrete substances that help heal simulated wounds in cell cultures, opening up new ways of delivering these substances to locations in the body where they can hasten healing.

The capsules need to be tested to see if they help healing in animals and humans, but they could eventually lead to living bandage technologies: wound dressings embedded with capsules of stem cells to help the wound regenerate.

Microencapsulated equine mesenchymal stromal cells promote cutaneous wound healing in vitro appeared in the April 10Stem Cell Research & Therapy.

The encapsulation seems to increase the stem cells regenerative potential, said Gerlinde Van de Walle of the Baker Institute for Animal Health in the College of Veterinary Medicine, adding that the reasons why are not yet known. It's possible that putting them in capsules changes the interactions between stem cells or changes the microenvironment.

To her knowledge, Van de Walle said, this is the first time encapsulated stem cells have been used to treat wounds. Her team used horse stem cells and cell cultures because, unlike mice, the healing process in horses shares important similarities with the healing process in humans and because wound healing in horses is a particularly difficult problem in veterinary medicine.

Mesenchymal stem cells are adult stem cells that can be isolated from different parts of the body, and its long been known that they secrete substances that aid in tissue healing. Problems arise when trying to use these stem cells in real patients, Van de Walle said, because they often wont stay put in the healing area and can occasionally form tumors or develop into unwanted cell types. She and her team began exploring the possibilities of encapsulating these cells as a way of avoiding these pitfalls. The capsules help cells stay in place while they secrete substances into the wound and can be removed easily if the stem cells would develop in an adverse way.

The researchers collaborated with Mingling Ma of the Department of Biological and Environmental Engineering and his laboratory to create the coreshell hydrogel microcapsules around the stem cells

Van de Walle says she was excited to see that the capsules did not abolish the stem cell properties but instead appeared to enhance the beneficial effects the stem cell secreted products have on tissue cultures. This suggests that encapsulating the stem cells for wound healing not only avoids certain problems, it can boost the effectiveness of treatment.

With their mesenchymal stem cell work, Van de Walle and her colleagues are trying to understand the basic science behind the regenerative abilities of these cells.

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Encapsulated stem cells accelerate wound healing

Human Stem Cells: A Potential Treatment for Huntington #39;s disease
Dr. Vicki Wheelock presents during Brain Awareness Week at University of California Davis Center for Neuroscience.

By: Center for Neuroscience, UC Davis

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Human Stem Cells: A Potential Treatment for Huntington's disease - Video

For millions of people around the world, who suffer from various diseases, research in stem cells offers a ray of hope. Scientists of the city-based Indian Institute of Science have used stem cells of a mouse to culture cardiac cells.

Explaining the research, Polani B. Seshagiri said their research over the past seven years has helped develop cardiac cells that function and beat in rhythms identical to the original cell.

Speaking on Stem Cell Awareness Day recently, Prof. Seshagiri said stem cells had several advantages and could cure human disorders and diseases, which could not be cured by conventional approaches. However, he warned that there was a need to be aware of the limitations of stem cells.

Sudarshan Ballal, Medical Director, Manipal Health Enterprise, said stem cells had enormous potential as they never die and could be converted into any cell. Stem cells can be converted into organs and maybe years later, organs can be cultivated in labs through stem cell, he said. Elaborating further, he said a stem cell could be compared to a bicycle, which could turn into car, motorbike and spaceship based on the environment and conditions.

Nazeer Ahmed, Deputy Drug Controller of Karnataka, said they were in the process of chalking out regulations for stem cells as there were currently no rules to regulate stem cell research and therapy.

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Scientists develop cardiac cells using stem cells

Targeted cancer therapies work by blocking a single oncogenic pathway to halt tumor growth. But because cancerous tumors have the unique ability to activate alternative pathways, they are often able to evade these therapies -- and regrow. Moreover, tumors contain a small portion of cancer stem cells that are believed to be responsible for tumor initiation, metastasis and drug resistance. Thus, eradicating cancer stem cells may be critical for achieving long-lasting remission, but there are no drugs available that specifically attack cancer stem cells.

Now a research team led by investigators in the Cancer Research Institute at Beth Israel Deaconess Medical Center (BIDMC), has identified an inhibitor of the Pin1 enzyme that can address both of these challenges in acute promyelocytic leukemia (APL) and triple negative breast cancer.

Their surprising discovery demonstrates that the vitamin A derivative ATRA (all-trans retinoic acid), a treatment for APL that is considered to be the first example of modern targeted cancer therapy, can block multiple cancer-driving pathways and, at the same time, eliminate cancer stem cells by degrading the Pin1 enzyme. Reported online in Nature Medicine, these novel findings suggest a promising new way to fight cancer -- particularly cancers that are aggressive or drug resistant.

"Pin1 changes protein shape through proline-directed phosphorylation, which is a major control mechanism for disease," explains co-senior author Kun Ping Lu, MD, PhD, Director of Translational Therapeutics in the Cancer Research Institute at BIDMC and Professor of Medicine at Harvard Medical School who co-discovered the enzyme in 1996. "Pin1 is a common key regulator in many types of cancer, and as a result, can control over 50 oncogenes and tumor suppressors, many of which are known to also control cancer stem cells."

Until now, agents that inhibit Pin1 have been developed mainly through rational drug design. Although these inhibitors have proven to be active against Pin1 in the test tube, when they are tested in vitro in a cell model or in vivo in a living animal they are unable to efficiently enter cells to successfully inhibit Pin1 function.

In this new work, co-senior author Xiao Zhen Zhou, MD, an investigator in BIDMC's Division of Translational Therapeutics and Assistant Professor at Harvard Medical School, decided to take a different approach to identify Pin1 inhibitors: She developed a mechanism-based high throughput screen to identify compounds that were targeting active Pin1.

"We had previously identified Pin1 substrate-mimicking peptide inhibitors," explains Zhou. "We therefore used these as a probe in a competition binding assay and screened approximately 8,200 chemical compounds, including both approved drugs and other known bioactive compounds." To increase screening success, Zhou chose a probe that specifically binds to the Pin1 enzyme active site very tightly, an approach that is not commonly used for this kind of screen.

"Initially, it appeared that the screening results had no positive hits, so we had to manually sift through them looking for the one that would bind to Pin1. We eventually spotted cis retinoic acid, which has the same chemical formula as all-trans retinoic acid [ATRA], but with a different chemical structure." It turned out, Zhou explains, that Pin1 prefers binding to ATRA and cis retinoic acid needs to convert ATRA in order to bind Pin1.

ATRA was first discovered for the treatment of acute promyelocytic leukemia (APL) in 1987. "Before tamoxifen or other targeted drugs, there was ATRA," says Lu. It was originally thought that ATRA was successfully treating APL by inducing cell differentiation, causing cancer cells to change into normal cells by activating the cellular retinoic acid receptors. But as these new findings reveal, although this differentiation activity is obvious, it is not the mechanism that is actually behind ATRA's successful outcomes in treating APL.

"While it has been previously shown that ATRA's ability to degrade the leukemia-causing fusion oncogene PML-RAR causes ATRA to stop the leukemia stem cells that drive APL, the underlying mechanism has remained elusive," says Lu. "Our new high throughput drug screening has revealed the ATRA drug target, unexpectedly showing that ATRA directly binds, inhibits and ultimately degrades active Pin1 selectively in cancer cells. The Pin1-ATRA complex structure suggests that ATRA is trapped in the Pin1 active site by mimicking an unreleasable enzyme substrate. Importantly, ATRA-induced Pin1 ablation degrades the fusion oncogene PML-RAR and treats APL in cell and animal models as well as in human patients.

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Researchers identify drug target for ATRA, the first precision cancer therapy

SAN DIEGO -

Two years ago, Brenda Guerra's life changed forever.

"They told me that I went into a ditch and was ejected out of the vehicle," Guerra said.

The accident left the 26-year-old paralyzed from the waist down and confined to a wheelchair.

"I don't feel any of my lower body at all," she said.

Guerra has traveled from Kansas to UC San Diego to be the first patient to participate in a groundbreaking safety trial, testing stem cells for paralysis.

"We are directly injecting the stem cells into the spine," said Dr. Joseph D. Ciacci, professor of neurosurgery at UC San Diego.

The stem cells come from fetal spinal cords. The idea is when they're transplanted they will develop into new neurons and bridge the gap created by the injury by replacing severed or lost nerve connections. They did that in animals, and doctors are hoping for similar results in humans. The ultimate goal is to help people like Guerra walk again.

"The ability to walk is obviously a big deal not only in quality of life issues, but it also affects your survival long-term," Ciacci said.

Guerra received her injection and will be followed for five long years. She knows it's only a safety trial, but she's hoping for the best.

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Health Beat: Stem cells for paralysis: 1st of its kind study

By Amy Norton HealthDay Reporter

FRIDAY, April 10, 2015 (HealthDay News) -- Two experimental therapies might help manage the inflammatory bowel disorder Crohn's disease, if this early research pans out.

In one study, researchers found that a fecal transplant -- stool samples taken from a healthy donor -- seemed to send Crohn's symptoms into remission in seven of nine children treated.

In another, a separate research team showed that stem cells can have lasting benefits for a serious Crohn's complication called fistula.

According to the Crohn's & Colitis Foundation, up to 700,000 Americans have Crohn's -- a chronic inflammatory disease that causes abdominal cramps, diarrhea, constipation and rectal bleeding. It arises when the immune system mistakenly attacks the lining of the digestive tract.

A number of drugs are available to treat Crohn's, including drugs called biologics, which block certain immune-system proteins.

But fecal transplants take a different approach, explained Dr. David Suskind, a gastroenterologist at Seattle Children's Hospital who led the new study.

Instead of suppressing the immune system, he said, the transplants alter the environment that the immune system is reacting against: the "microbiome," which refers to the trillions of bacteria that dwell in the gut.

Like the name implies, a fecal transplant involves transferring stool from a donor into a Crohn's patient's digestive tract. The idea is to change the bacterial composition of the gut, and hopefully quiet the inflammation that causes symptoms.

And for most kids in the new study, it seemed to work. Within two weeks, seven of nine children were showing few to no Crohn's symptoms. Five were still in remission after 12 weeks, with no additional therapy, the researchers reported in a recent issue of the journal Inflammatory Bowel Diseases.

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Stem Cells, Fecal Transplants Show Promise for Crohn's Disease

Two experimental therapies might help manage the inflammatory bowel disorder Crohn's disease, if this early research pans out.

In one study, researchers found that a fecal transplant -- stool samples taken from a healthy donor -- seemed to send Crohn's symptoms into remission in seven of nine children treated.

In another, a separate research team showed that stem cells can have lasting benefits for a serious Crohn's complication called fistula.

According to the Crohn's & Colitis Foundation, up to 700,000 Americans have Crohn's -- a chronic inflammatory disease that causes abdominal cramps, diarrhea, constipation and rectal bleeding. It arises when the immune system mistakenly attacks the lining of the digestive tract.

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Hundreds of thousands of people suffer from the potentially life threatening C. difficile bacterial infection in their intestines. CBS News' Marl...

A number of drugs are available to treat Crohn's, including drugs called biologics, which block certain immune-system proteins.

But fecal transplants take a different approach, explained Dr. David Suskind, a gastroenterologist at Seattle Children's Hospital who led the new study.

Instead of suppressing the immune system, he said, the transplants alter the environment that the immune system is reacting against: the "microbiome," which refers to the trillions of bacteria that dwell in the gut.

Like the name implies, a fecal transplant involves transferring stool from a donor into a Crohn's patient's digestive tract. The idea is to change the bacterial composition of the gut, and hopefully quiet the inflammation that causes symptoms.

Read the original here:
Fecal transplant, stem cells may help Crohn's disease