In our search for stem cell therapies that target the central nervous system, we use a multidisciplinary approach that involves molecular biology, biochemical techniques and stem cell transplantation. We seek to identify the best sources of stem cells for various therapies, combinatory therapies strategies, that will synergize with stem cell modalities, determine the mechanisms involved in stem cell migration, and describe the inflammatory components that contribute to the symptoms of these diseases.
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Neural stem cells are the most primordial and least committed cells of the nervous system. They possess the capacity to self-renew and can generate neural cells such as neurons, astrocytes, and oligodendrocytes. Neural stem cells possess a range of actions that are potentially therapeutic, either by cell replacement or as vehicles to deliver therapeutic gene products synthesized by the stem cells.
The therapeutic potential of stem cells offers great hope for curing or easing devastating diseases that are presently untreatable. Neurodegenerative diseases attack the central nervous system and are very difficult to treat. These diseases can strike throughout life, with Tay-Sachs and Sandhoff disease occurring in early childhood, while Alzheimer’s and Parkinson's disease, stroke, and multiple sclerosis, are adult diseases related to aging.
To identify the most promising stem cell therapies, we transplant stem cells from various sources into mice that are genetically predisposed to develop neurodegenerative diseases. The types of human neural stem cells we are evaluating include cells isolated directly from the central nervous system and indirectly derived from nonneural stem cells such as embryonic stem cells or induced pluripotent stem cells (iPSCs). Human iPSCs are derived from readily available adult somatic cells such as foreskin fibroblasts, by forced expression of specific Genes. IPSCs present fewer ethical and immune issues compared with embryonic stem cells. While iPSCs are known to emulate embryonic stem cells, we are currently optimizing experimental conditions to assure that iPSCs are true stem cell equivalents in terms of cell functionality and phenotype.
To find more powerful and effective treatments than can be achieved with a single approach, we are also developing combination therapies strategies that can enhance stem cell action. Such combinatorial treatments may include using multiple stem cell types, including bone marrow stem cells (combining cell strategy), or jointly administering stem cell therapies with pharmacological approaches.