Scientists Aim to Use Embryonic Stem Cells for Chronic Pain

Chronic pain, by definition, is difficult to manage, but a new study by UCSF scientists shows how a cell therapy might one day be used not only to quell some common types of persistent and difficult-to-treat pain, but also to cure the conditions that give rise to them.

The researchers, working with mice, focused on treating chronic pain that arises from nerve injury — so-called neuropathic pain.

In their study, published in the May 24, 2012 issue of Neuron, the scientists transplanted immature embryonic nerve cells that arise in the brain during development and used them to make up for a loss of function of specific neurons in the spinal cord that normally dampen pain signals.

A small fraction of the transplanted cells survived and matured into functioning neurons. The cells integrated into the nerve circuitry of the spinal cord, forming synapses and signaling pathways with neighboring neurons.

As a result, pain hypersensitivity associated with nerve injury was almost completely eliminated, the researchers found, without evidence of movement disturbances that are common side effects of the currently favored drug treatment.

“Now we are working toward the possibility of potential treatments that might eliminate the source of neuropathic pain, and that may be much more effective than drugs that aim only to treat symptomatically the pain that results from chronic, painful conditions,” said the senior author of the study, Allan Basbaum, PhD, chair of the Department of Anatomy at UCSF.

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Scientists bypass stem cells to create nervous system cells

Mouse skin cells can be converted directly into cells that become the three main parts of the nervous system, according to researchers at the Stanford University School of Medicine. The finding is an extension of a previous study by the same group showing that mouse and human skin cells can be directly converted into functional neurons.

The multiple successes of the direct conversion method could refute the idea that pluripotency (a term that describes the ability of stem cells to become nearly any cell in the body) is necessary for a cell to transform from one cell type to another. Together, the results raise the possibility that embryonic stem cell research and another technique called “induced pluripotency” could be supplanted by a more direct way of generating specific types of cells for therapy or research.

This new study, published online Jan. 30 in the Proceedings of the National Academy of Sciences, is a substantial advance over the previous paper in that it transforms the skin cells into neural precursor cells, as opposed to neurons. While neural precursor cells can differentiate into neurons, they can also become the two other main cell types in the nervous system: astrocytes and oligodendrocytes. In addition to their greater versatility, the newly derived neural precursor cells offer another advantage over neurons because they can be cultivated to large numbers in the laboratory — a feature critical for their long-term usefulness in transplantation or drug screening.

In the study, the switch from skin to neural precursor cells occurred with high efficiency over a period of about three weeks after the addition of just three transcription factors. (In the previous study, a different combination of three transcription factors was used to generate mature neurons.) The finding implies that it may one day be possible to generate a variety of neural-system cells for transplantation that would perfectly match a human patient.

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Stem Cell Survival Strategy Is Key to Blood and Immune System Health

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Stem cells of the aging bone marrow recycle their own molecules to survive and keep replenishing the blood and immune systems as the body ages, researchers at UC San Francisco (UCSF) have discovered.

The recycling process, known as autophagy, or self-eating, involves reusing molecules and the chemical energy obtained from these molecules to withstand the killing effect of metabolic stress that intensifies as the body ages.

The discovery, reported online Feb. 6 in the journal Nature, showed that autophagy allows stem cells to avoid the alternative response to stress, which is programmed cellular suicide, in which cells that aren’t up to snuff kill themselves for the greater good.

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Scientists Identify Critical Process in Stem Cell Development

Scientists at the Gladstone Institutes have discovered that environmental factors critically influence the growth of a type of stem cell — called an iPS cell — that is derived from adult skin cells. This discovery offers newfound understanding of how these cells form, while also advancing science closer to stem cell-based therapies to combat disease.

Researchers in the laboratory of Gladstone Senior Investigator Shinya Yamanaka, MD, PhD, have for the first time shown that protein factors released by other cells affect the “reprogramming” of adult cells into stem cells known as induced pluripotent stem cells, or iPS cells. The scientists — who collaborated on this research with colleagues from the University of California, San Francisco (UCSF) — announce their findings today online in Cell Stem Cell.

In 2007, Dr. Yamanaka discovered a recipe of specific proteins to add to human skin cells as a way to induce them into becoming iPS cells — which act very much like embryonic stem cells. Many see iPS cell technology as a new platform for drug discovery and the study of disease fundamentals — while avoiding the ethical issues surrounding research involving embryonic stem cells. But questions remain about the most efficient way to cultivate iPS cells.

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New Stem Cell Activity in Human Brain Identified

A novel pathway of stem cell activity in human brain that represents potential targets of brain injuries affecting newborns has been identified by researchers at Barrow Neurological Institute at St. Joseph’s Hospital and Medical Center. The recent study, which raises new questions of how the brain evolves, is published in the current issue of Nature, one of the world’s most cited scientific journals.

Nader Sanai, MD, director of Barrow’s Brain Tumor Research Center, led this study, which is the first developmental study of human neural stem cells in a region of the brain called the subventricular zone, the tissue structure in which brain stem cells reside. Also participating in the study were researchers from University of California San Francisco and the University of Valencia in Spain.

The findings revealed that there is a pathway of young migrating neurons targeting the prefrontal cortex of the human brain in the first few months of life. After the first year of life, the subventricular zone of the brain slows down, tapering production of new brain cells by the time a child is 18-months and then to nearly zero by age two. This revelation settles conflicting prior reports that suggested that human neural stem cell cells remain highly active into adulthood.

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