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

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 溶酶体贮积病是一组异质性疾病，其特征在于在身体的许多器官中分解代谢物所必需的几种酶之一中的遗传缺陷。 在某些情况下，酶缺乏对中枢神经系统（CNS）有深远的影响，导致进行性神经变性和过早死亡。 没有标准疗法可以延迟或预防与溶酶体贮积病相关的神经系统后遗症。 本项目的总体目标是评估骨髓间充质干细胞（MSC）的直接颅内移植是否能有效延迟Krabbe病的非人灵长类动物模型的发病或延缓神经变性。 在此，将MSC直接注射到幼年恒河猴的CNS中，并量化总体细胞植入水平，并绘制其在脑中的解剖分布。 这些数据与对动物健康、发育、行为和运动技能的影响相关，以评价整体方法的安全性。 此外，由于在大多数情况下MSC来源于无关供体，因此将监测每个移植受体的免疫状态以评估宿主对移植物的耐受性。 一旦确定了最佳的细胞移植参数，将MSC移植到患有Krabbe病的婴儿猕猴中，并评估对疾病进展的影响。 通过采用相关的大型动物模型，从这些研究中获得的数据将有助于开发更有效的治疗患有溶酶体贮积病的人类婴儿神经系统后遗症的疗法。

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.