Stem cell biology in degenerative disease and cancer
1. Previous and current research
Relative to most organs, the brain has very limited regenerative potential. But within it, a population of immature cells persists in adulthood, suggesting that it, too, possesses an innate ability to repair itself. These cells are termed neural stem cells and are considered immature because they have not fulfilled their developmental options; instead, they have maintained their ability to proliferate, and have kept open their options to mature into any one of the main cell types of the brain (neurons, astrocytes, or oligodendrocytes).
In mammals, adult neural stem cells were first discovered in two small areas of the rodent brain, the subventricular zone, and the dentate gyrus of the hippocampus. In these areas, neural stem cells are able to proliferate and some of the new cells mature to become neurons. This may be a mechanism to provide new neurons throughout the lifespan of the animal in areas that are involved with olfaction, learning, and memory [all experience-based processes with a need to register information].
But we recently showed that in the adult brain and spinal cord, neural stem cells are plentiful and widespread. We address the question of their function to understand how they can be coaxed to help in disease. To do so, we study the mechanisms that regulate stem cell survival and proliferation, and as a consequence, their numbers. We have discovered that these cells use biochemical pathways in distinct ways than most mature cell types in the body, and we have found pharmacological means to regulate their numbers. This has provided a tool to study their role in the context of neurodegenerative diseases such as Parkinson’s disease, and brain insults such as ischemic stroke.
We found that a variety of treatments that increase the numbers of these cells result in the dramatic rescue of neurons that would otherwise die due to disease. We think this is because neural stem cells physically associate with neurons and produce factors that support their survival. Our results show that great benefits can be achieved by targeting the endogenous population of neural stem cells, and encouraging them to protect injured neurons.
2. Future Prospects and goals
Our efforts are focused on uncovering additional facets of the signals that regulate neural stem cells in order to devise new treatments, including ones that can be used clinically. This requires basic research into the mechanisms that control stem cell survival and proliferation. Recently, we showed that cholera toxin, which regulates a number of cellular functions also regulates the biochemical pathways we previously discovered and greatly increases stem cell numbers in culture.
We are also interested to expand the scope of our work beyond the nervous system and into other organs, such as the pancreas, because we have shown that many of the core principles that regulate stem cells from the brain are shared by other tissues. This effort could lead to therapeutic strategies that aim to stop the degeneration of tissues and not merely treat symptoms.
A more comprehensive and technical description of our findings can be found following this link:
Stem Cell Biology Research - www.innaterepair.net
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|| Group Leader, Medical Clinc III, University of Dresden.
||Staff Scientist, National Institute of Neurological Diseases and Stroke, National
Institutes of Health, USA.
||Research Fellow, National Institute of Neurological Diseases and Stroke, National
Institutes of Health, USA.
||Postdoctorate fellow, Dept. of Pharmacology, Yale University.
||PhD, Imperial College of Science, Technology, and Medicine, University of London, UK.
||BSc, Imperial College of Science, Technology, and Medicine, University of London, UK.|