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

间充质干细胞对恒河猴中枢神经系统给药的安全性

• 批准号: 8357935
• 负责人: Donald G Phinney
• 金额: $ 5.4万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357935
• 关键词: Affect; Anatomy; Animal Model; Animals; Behavior; Bone Marrow Transplantation; Brain; Cell Transplantation; Cells; Cessation of life; Data; Development; Disease; Disease Progression; Engraftment; Enzymes; Funding; Genetic; Globoid cell leukodystrophy; Goals; Grant; Health; Human; Immune; Infant; Lysosomal Storage Diseases; Macaca; Macaca mulatta; Maps; Mesenchymal Stem Cells; Modeling; Monitor; Motor Skills; National Center for Research Resources; Neuraxis; Neurologic; New England; Organ; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Safety; Source; Transplant Recipients; Transplantation; United States National Institutes of Health; base; cost; enzyme deficiency; nonhuman primate; premature; prevent

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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 溶酶体贮积病是一组异质性疾病，其特征是体内许多器官代谢物分解所必需的几种酶之一的遗传缺陷。 在某些情况下，酶缺乏会对中枢神经系统（CNS）产生深远影响，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。 该项目的总体目标是评估直接颅内移植骨髓间充质干细胞（MSC）是否能有效延迟克拉伯病的非人类灵长类动物模型的发病或延缓神经变性。 在此，间充质干细胞将被直接注射到幼年恒河猴的中枢神经系统中，并对整体细胞植入水平进行量化，并绘制它们在大脑中的解剖分布图。 这些数据与对动物健康、发育、行为和运动技能的影响相关，以评估整体方法的安全性。 此外，由于在大多数情况下，间充质干细胞来自无关的供体，因此将监测每个移植受者的免疫状态，以评估宿主对移植物的耐受性。 一旦确定了最佳细胞移植参数，间充质干细胞将被移植到患有克拉伯病的幼年猕猴中，并评估对疾病进展的影响。 通过使用从这些研究中获得的相关大型动物模型数据，将有助于开发更有效的疗法来治疗患有溶酶体贮积病的人类婴儿的神经系统后遗症。