This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.This proposal aims to assess in a relevant animal model the safety, feasibility and efficacy of adult stem cell administration to the CNS for treating neurological sequelae associated with lysosomal storage diseases. Specifically, adult stem cells derived from bone marrow, referred to as mesenchymal stem cells (MSCs) have been injected unilaterally into the caudate putamen of infant rhesus macaques (Macaca mulatta) using stereotaxic coordinates determined by MRI. Prior to and at various periods up to 1 year post-transplantation, the health, development, behavior as well as cogntive and motor skills of each transplant recipient will be evaluated using a battery of age appropriate tests and compared to sham-operated animals or normative control data. Additionally, the levels and anatomical distribution of male MSCs engrafted in the CNS of female transplant recipients were evaluated using a real-time PCR assay we developed that targets sequences in the Macaca sp. Y chromsome. To confirm the real-time PCR data engrafted MSCs were visualized in brain sections by immunofluorescent staining or FISH and counted using modern stereological techniques. Correlating MSC engraftment in brain with long-term affects on health, development, behavior and motor function will directly assess the safety and feasibility of intracranial MSC administration. Collectively, these proposed studies will yield important pre-clinical safety and toxicology data in a relevant animal model that will be essential for developing stem cell-based therapies to treat neurological sequelae in human infants and children afflicted with various lysosomal storage diseases.
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