CNS Plasticity of Human Adipo-derived Multipotent Cells

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DESCRIPTION (provided by applicant): Stem cells and regenerative cell therapies hold great promise for treating a variety of disorders; however, an optimal cell source for translating this promise into the clinical realm remains to be determined. The use of embryonic stem cells is fraught with ethical and political controversy, and these cells present several practical issues, including adequacy of supply and non-autologous tissue responses. Adult stem cells offer a less controversial, and potentially autologous, solution; but their utility may be restricted by a limited range of developmental plasticity and an inadequacy of supply. An ideal source of cells would be abundant, expendable, replenishable, autologous, and should be easy and safe to harvest. The cells should possess considerable growth capacity, developmental plasticity, and ideally would be free of ethical and political constraints. Recently, we have demonstrated the existence of multipotent cells within human subcutaneous adipose tissue. These cells have the capacity for extensive growth, renewal, and can differentiate in vitro along ectodermally and mesodermally derived lineages. Moreover, adipose tissue represents an abundant, autologous source of cells, which can be easily and safely harvested. The studies proposed in this R21 application will investigate the plasticity of adult human adipo-derived cells (hADCs) in the rat central nervous system, hADCs are capable of differentiating into cells with neural phenotypes in vitro. Preliminary findings indicate that hADCs survive injection into the brain, migrate long distances in naive and injured (post-ischemic) brains, exhibit targeted migration to regions of injury, and survive for at least 10 weeks in vivo (the longest period tested to date). The central hypothesis of this application is that hADCs can engraft and migrate in the central nervous system, exhibit targeted migration to areas of cerebral injury, differentiate into neural cell types, and exhibit long-term survival. This hypothesis will be evaluated in the context of two specific aims. Aim 1 will identify the phenotypic and positional fates of hADCs implanted into the CNS of naive (i.e. uninjured) rats. Aim 2 will identify the phenotypic and positional fates of hADCs implanted into rat CNS after injurious transient ischemia. The results of these studies will provide the first evidence of hADC plasticity in the brain and could form the foundation for future cell-based therapies in the CNS.