Stem Cell Research

Astrocytes Control Generation Of New Neurons From Neural Stem Cells

New research has shown how astrocytes control the generation of new neurons in the brain. Earlier research in the same laboratory demonstrated that astrocytes reduce brain tissue damage after stroke and that the integration of transplanted neural stem cells can be largely improved by modulating the activity of astrocytes.

“In the brain, astrocytes control how many new neurons are formed from neural stem cells and survive to integrate into the existing neuronal networks, said Milos Pekny, Professor and Laboratory Director, Center for Brain Repair and Rehabilitation, Dept. of Clinical Neuroscience and Rehabilitation, University of Gothenburg. "Astrocytes do this by secreting specific molecules but also by much less understood direct cell-cell interactions with stem cells.”

Blood-Brain Barrier Building Blocks Generated From Human Stem Cells

The blood-brain barrier -- the filter that governs what can and cannot come into contact with the mammalian brain -- is a marvel of nature. It effectively separates circulating blood from the fluid that bathes the brain, and it keeps out bacteria, viruses and other agents that could damage it.

However, the barrier can be disrupted by disease, stroke and multiple sclerosis, for example, and also is a big challenge for medicine, as it can be difficult or impossible to get therapeutic molecules through the barrier to treat neurological disorders.

Now researchers have transformed stem cells into endothelial cells with blood-brain barrier qualities in a laboratory dish in an attempt to get the blood-brain barrier to share its secrets.

“The nice thing about deriving endothelial cells from induced pluripotent stem cells is that you can make disease-specific models of brain tissue that incorporate the blood-brain barrier,” explains Sean Palecek, a UW-Madison professor of chemical and biological engineering. “The cells you create will carry the genetic information of the condition you want to study.”

In Step Toward Alzheimer's Therapy, Neural Stem Cells Induced From Transfer Of Single Gene Form Interconnected, Functional Network Of Brain Cells

This research comes at a time of renewed focus on Alzheimer's disease which currently afflicts 5.4 million people in the United States alone—a figure expected to nearly triple by 2050. There are no approved medications to prevent or reverse the progression of this debilitating disease.

A single gene, Sox2, was transferred into both mouse and human skin cells. Within days the skin cells transformed into early-stage brain stem cells, also called induced neural stem cells (iNSCs). These iNSCs began to self-renew, soon maturing into neurons capable of transmitting electrical signals. Within a month, the neurons had developed into neural networks.

“Many drug candidates—especially those developed for neurodegenerative diseases—fail in clinical trials because current models don't accurately predict the drug's effects on the human brain,” said Dr. Yadong Huang, MD, PhD, Gladstone Institutes researcher and associate professor of neurology at the University of California, San Francisco (UCSF), with which Gladstone is affiliated. “Human neurons—derived from reengineered skin cells—could help assess the efficacy and safety of these drugs, thereby reducing risks and resources associated with human trials.”

Video: Lawrence Goldstein -- Evidence-based Development of Stem Cell Therapies

As we move forward in clinical trials for autologous and allogeneic stem cell therapies, recognition of what we don't know and what we do is both critical and constantly changing. The integration of this expanding stem cell knowledge with the parallel expansion of our knowledge of the biochemestry and molecular biology of the human body will hopefully produce continually improving therapies. However, the acquisition of knowledge and understanding is not linear. Research in therapies can get ahead of our understanding of disease process and have. This video is a reality check on what we know of neurodegenerative disease and potential therapy as of October 2011. It is well worth watching.

Taking place at the World Stem Cell Summit, this talk is about 37 minutes long. With an emphasis on Alzheimer's disease, Dr. Goldstein does a truly excellent job of pointing out the difficulty of understanding

Blood Stem Cell Growth Factor Found to Reverse Memory Decline in Mice

A human growth factor that stimulates blood stem cells to proliferate in the bone marrow reverses memory impairment in mice genetically altered to develop Alzheimer's disease, researchers at the University of South Florida have found. The granulocyte-colony stimulating factor (GCSF) significantly reduced levels of the brain-clogging protein beta amyloid deposited in excess in the brains of the Alzheimer's mice, increased the production of new neurons and promoted nerve cell connections.

GCSF is a blood stem cell growth factor or hormone routinely administered to cancer patients whose blood stem cells and white blood cells have been depleted following chemotherapy or radiation. GCSF stimulates the bone marrow to produce more white blood cells needed to fight infection. It is also used to boost the numbers of stem cells circulating in the blood of donors before the cells are harvested for bone marrow transplants. Advanced clinical trials are now investigating the effectiveness of GCSF to treat stroke, and the compound was safe and well tolerated in early clinical studies of ischemic stroke patients.

"GCSF has been used and studied clinically for a long time, but we're the first group to apply it to Alzheimer's disease," said USF neuroscientist Juan Sanchez-Ramos, MD, PhD, the study's lead author. "This growth factor could potentially provide a powerful new therapy for Alzheimer's disease – one that may actually reverse disease, not just alleviate symptoms like currently available drugs."

Medicine's New Toolbox: MIT's View Of Induced Pluripotency's Future

"The past two years have been nothing short of a revolution," says John Dimos, a senior scientist at iZumi Bio. "These cells didn't really exist two years ago. This is all brand-new technology, and it's opening up the potential for brand-new science." The company John is with, Izumi Bio, plans to take advantage of that potential by developing a bank of iPS cells from patients with various diseases and using the cells to screen candidates for drug development.

As a postdoc at Harvard, John Dimos built a cellular model of ALS (amyotrophic lateral sclerosis - Lou Gherig's Disease), making it possible to study a neurodegenerative disease outside an animal for the first time. He and his colleagues collected skin cells from an 82-year-old woman with ALS, reprogrammed them into iPS cells, and directed the cells to differentiate into motor neurons that were genetically identical to the donor's defective cells. "It was the first paper to show that you can use a stem cell to see disease pathology in a petri dish," says Douglas Melton, codirector of the Harvard Stem Cell Institute. "That means you can now study diseases in petri dishes and not in people. That's huge."

A First: Embryonic Stem Cells Coaxed To Become Nerve Cells

One of the most difficult challenges in stem cell research is figuring out exactly what biological events cause stem cells to differentiate into specific, functioning cells in the body.  For nerve cells this mystery may now be solved. For the first time, researchers have genetically programmed embryonic stem (ES) cells to become nerve cells when transplanted into the brain.

Stroke, Alzheimer’s, Parkinson’s and Huntington’s disease destroy brain cells, causing speech and memory loss and other debilitating consequences. Transplanting neuronal brain cells could restore at least some brain function, just as heart transplants restore blood flow.  But until now there has been no reliable method of coaxing stem cells to become nerve cells.

“We found that we could create new nerve cells from stem cells, transplant them effectively and make a positive difference in the behavior of the mice,” said Stuart A. Lipton, M.D., Ph.D., professor and director of the Del E. Webb Neuroscience, Aging, and Stem Cell Research Center at The Burnham Institute. “These findings could potentially lead to new treatments for stroke and neurodegenerative diseases such as Parkinson’s disease.”