SAFETY OF MESENCHYMAL STEM CELL ADMINISTRATION TO THE CNS OF RHESUS MACAQUES

Harvard Medical School, Boston MA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Lysosomal storage diseases are a heterogeneous group of disorders characterized by a genetic deficiency in one of several enzymes that are necessary for the breakdown of metabolites in many organs of the body. In some cases the enzyme deficiency has a profound effect on the central nervous system (CNS), leading to progressive neuro-degeneration and premature death. No standard therapies are available that can delay or prevent neurologic sequelae associated with lysosomal storage diseases. The overall goal of this project is to evaluate if direct intracranial transplantation of bone marrow-derived mesenchymal stem cells (MSCs) is efficacious in delaying the onset or retarding neuro-degeneration in a non-human primate model of Krabbe disease. Herein, MSCs will be injected directly into the CNS of infant Rhesus macaques and overall cell engraftment levels quantified and their anatomic distribution mapped in the brain. These data are correlated with effects on animal health, development, behavior, and motor skills to evaluate the safety of the overall approach. Additionally, since in most cases the MSCs are derived from an unrelated donor, the immune status of each transplant recipient will be monitored to evaluate host tolerance to the graft. Once optimal cell transplantation parameters are determined, MSCs will be transplanted into infant macaques afflicted with Krabbe disease and affects on disease progression evaluated. By employing a relevant large animal model data obtained from these studies will aide in developing more efficacious therapies for treating neurologic sequelae in human infants afflicted with lysosomal storage diseases.