Stem Cell Research: The Quest Resumes

Scientific inspiration can come from anywhere — a person, an event, even an experiment gone awry. But perhaps nothing can drive innovation more powerfully than the passion born of tragedy. Or, in Douglas Melton’s case, near tragedy. The co-director of the Harvard Stem Cell Institute (HSCI) is one of the leading figures in the search for cures for presently incurable diseases, and his breakthrough work is challenging many long-held beliefs about the ways biology and human development work.

But it was a very personal experience that brought Melton to stem cells, one that 17 years later he still finds difficult to discuss. When his son Sam was 6 months old, he became ill with what his parents thought was a cold. He woke up with projectile vomiting and before long began taking short, shallow breaths. After several hours, he started to turn gray, and Melton and his wife Gail brought the baby to the emergency room. For the rest of that afternoon, doctors performed test after test, trying to figure out what was wrong. “It was a horrific day,” says Melton. (See the top 10 medical breakthroughs of 2008.)

It was not until that evening that a nurse thought to dip a testing strip into Sam’s urine and they finally got a diagnosis. The boy’s body was flooded with sugar; he had Type 1 diabetes. Then, as now, the disease had no cure, and patients like Sam need to perform for themselves the duties their pancreas cannot — keeping track of how much glucose they consume and relying on an insulin pump to break down the sugars when their levels climb too high. The diagnosis changed not only Sam’s life but the lives of his parents and older sister Emma as well. Throughout Sam’s childhood, Gail would wake every few hours during the night to check his blood sugar and feed him sugar if his concentration fell too low or give him insulin if it was too high. “I thought, This is no way to live,” says Melton. “I decided I was not just going to sit around. I decided I was going to do something.”

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Researchers directly turn mouse skin cells into neurons

Marius Wernig

Even Superman needed to retire to a phone booth for a quick change. But now scientists at the Stanford University School of Medicine have succeeded in the ultimate switch: transforming mouse skin cells in a laboratory dish directly into functional nerve cells with the application of just three genes. The cells make the change without first becoming a pluripotent type of stem cell — a step long thought to be required for cells to acquire new identities.

The finding could revolutionize the future of human stem cell therapy and recast our understanding of how cells choose and maintain their specialties in the body.

“We actively and directly induced one cell type to become a completely different cell type,” said Marius Wernig, MD, assistant professor of pathology and a member of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine. “These are fully functional neurons. They can do all the principal things that neurons in the brain do.” That includes making connections with and signaling to other nerve cells — critical functions if the cells are eventually to be used as therapy for Parkinson’s disease or other disorders.

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How To Heal Diabetes Using Stem Cells

'Diabetes causes amputations', warns poster
Image by engineroomblog via Flickr

Using skin cells from people with type 1 diabetes, researchers were able to produce cells that made insulin in response to changing blood sugar levels, though not as efficiently as normal insulin-producing cells do. (…) “This is a big deal,” said Susan Solomon, CEO of the New York Stem Cell Foundation, which provided some of the funding for the study. “Tackling the basic biology of type 1 diabetes, which is a very complex disease, is a critical step. With these cells, we can see in a dish what’s happening to the immune system, and if you don’t understand the immune response, you get nowhere with type 1 diabetes.”

“This is very preliminary data, but now we could potentially look at the interaction between immune system cells and insulin-producing cells to find the root cause or trigger, which we think might vary from patient to patient,” explained Meri Firpo, an assistant professor at the Stem Cell Institute at the University of Minnesota (…)

In the current study, researchers from the Howard Hughes Medical Institute at the Harvard Stem Cell Institute and the Naomi Berrie Diabetes Center at Columbia University, obtained skin samples from two white males who had type 1 diabetes. One was diagnosed at 3 years of age, while the other was first diagnosed when he was 21.

Normal skin cells are already specialized cells. Their job is to protect the body with a covering of skin, explained Firpo. To transform these cells into embryonic-like stem cells, essentially getting them back to the beginning when they weren’t already specialized, researcher Doug Melton and his colleagues used three inserted genes to reprogram the cells, creating what’s known as an induced pluripotent stem cell (iPS). In this case, the cells were then turned into insulin-producing cells (…)

She said that this study helps further at least two areas of research that JDRF is focusing on: developing a self-source for islet-cell transplants and blocking the immune response. Another area of research that JDRF is actively pursuing is the possible encapsulation of islet cells before transplantation so that they could hide from the immune system (…)

from http://www.ajc.com/health/content/shared-auto/healthnews/diab/630511.html

A study published today in the Proceedings of the National Academy of Sciences describes a way to create induced pluripotent stem (iPS) cells from ordinary adult cells taken from patients with type 1 diabetes. These stem cells then can be reprogrammed to produce all of the cell types relevant to the disease.

“What you get is the ability to watch, for the first time, type 1 diabetes develop,” says senior author Douglas Melton, a professor of natural sciences at Harvard University and co-director of the Harvard Stem Cell Institute. “Until you watch a disease develop, you will not understand the mechanism, and you therefore cannot devise any kind of sensible treatment or cure.”

Melton and his colleagues show that the reprogrammed iPS cells–so called for their ability to give rise to many cell types–can be spurred to differentiate into tissue resembling the insulin-producing pancreatic beta cells that are destroyed by the immune system in type 1 diabetes.

Embryonic stem (ES) cells have long been the gold standard for deriving pluripotent cell lines. But ES cells can only be used to create disease models for disorders such as cystic fibrosis, where the genetic underpinnings are straightforward. Because the genetics underlying type 1diabetes are complex and poorly understood, researchers have no way to identify diabetes-specific ES cells (…)

Ultimately, Melton plans to construct a “living test tube” for probing the interplay between the beta cells and the immune system in diabetes. He hopes to use the diabetic iPS cells to generate all three relevant cell types and then to put those cells into a so-called humanized mouse that can accept human cells to see how they interact.

from http://www.technologyreview.com/biomedicine/23335/

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New BCM McNair Scholar applies stem cell technology to advance diabetes research

Stem cell and regenerative medicine expert Dr. Malgorzata Borowiak has been named Baylor College of Medicine‘s fifth McNair Scholar. She will focus on diabetes.

Using stem cell technology, Borowiak’s research focuses on understanding the mechanisms of type 1 diabetes to identify new, cellular treatments for the disease.

The McNair Scholar program at BCM, supported by the Robert and Janice McNair Foundation and managed by the McNair Medical Institute, identifies outstanding scientists and physician scientists in biomedical research in four areas – breast cancer, pancreatic cancer, juvenile diabetes and neuroscience.

Borowiak, who started at BCM in January, serves as an assistant professor of molecular and cellular biology and as a member of the Stem Cells and Regenerative Medicine Center at BCM and the Center for Cell and Gene Therapy at BCM, Texas Children’s Hospital and The Methodist Hospital.

“We are very excited to welcome Dr. Borowiak, who will act as the crucial ‘missing-link’ in our program to develop stem cell therapy for diabetes,” said Dr. Malcolm Brenner, director of the Center for Cell and Gene Therapy.

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