P3-ADULT BONE MARROW STEM CELLS FOR CNS REPAIR

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Adult stem cells from bone marrow have the potential to provide powerful new treatments for central nervous system (CNS) disorders. Currently it is unclear which cells or sub-populations will be best suited to effectively treat a variety of diseases that may be amenable to such a therapeutic approach. Furthermore, in addition to the standard paradigm of stem cell engraftment, differentiation, and replacement of damaged cells, several reports in the literature, as well as our preliminary data, suggest that the secretion of neurotrophic factors by transplanted adult stem cells may play the principal role in their mediation of CNS repair. The identification of a bone marrow-derived stem cell sub-population that is best suited for neuroprotection or repair would be of great potential clinical importance. We have proposed a series of experiments to test the central hypothesis that an optimized population of paracrine-acting adult stem cells from bone marrow can be used for CNS repair. The specific aims are: 1. To determine whether specific populations of adult bone marrow stem cells secrete growth factors with known neurotrophic activities. 2. To determine whether transplantation of the "high neurotrophin population" of marrow stem cells activates endogenous mouse CNS cells, including endogenous stem cells. 3. To determine whether the "high neurotrophin population" of marrow stem cells affects neuronal survival and activates endogenous stem cells in brain after ischemic stroke.