Motor and Cognitive Recovery Induced by Bone Marrow Stem Cells Grafted to Striatum and Hippocampus of Impaired Aged Rats: Functional and Therapeutic Considerations

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Abstract
Impairments in motor coordination and cognition in normal and pathological aging are often accompanied by structural changes, that is, loss of synapses and neurons. Also, it has been shown recently that bone marrow stem cells can give origin to cells of different tissues, including neural cells. Given the therapeutic implications of increasing health and functional possibilities in the aged brain, we have tested the effects of rat femur bone marrow stem cells (rBMSCs) grafting to the striatum hippocampus of aged rats with motor or cognitive deficits, respectively. Bone marrow cells were transduced with an adenovirus driving the expression of green fluorescence protein (GFP) and other classic stains to determine their migration, engraftment, differentiation, and associated behavioral recovery. Five weeks after it, control and grafted rats were re-evaluated with the Morris Water Maze test, Passive avoidance, open-field, motor coordination, and Marshall tests and perfused. Brains were processed and analyzed for fluorescent protein expression. GFP was detected in cells with some differentiation degree into neural-like cells. Their exact phenotype is yet to be determined. A significant functional recovery was observed 6 weeks after grafting, suggesting a trophic interaction between rBMSCs and the aged/dystrophic host brain, or with the host brain progenitor cells and/or by increasing the number of functional cells at striatum or hippocampus, suggesting that the aging brain keeps its functional plasticity as well as that BMSCs are interesting candidates for cell replacement therapies in neurodegenerative disorders.