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: 8172844
• 负责人: Donald G Phinney
• 金额: $ 6.58万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172844
• 关键词: Affect; Anatomy; Animal Model; Animals; Behavior; Bone Marrow; Brain; Cell Transplants; Cessation of life; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Disease; Disease Progression; Engraftment; Enzymes; Funding; Genetic; Globoid cell leukodystrophy; Goals; Graft Rejection; Grant; Health; Human; Immune; Infant; Institution; Lysosomal Storage Diseases; Macaca; Macaca mulatta; Mesenchymal Stem Cells; Monitor; Motor Skills; Nerve Degeneration; Nervous system structure; Neuraxis; Organ; Research; Research Personnel; Resources; Safety; Source; Stem cell transplant; Stem cells; Transplant Recipients; United States National Institutes of Health; enzyme activity; enzyme deficiency; nonhuman primate; premature; prevent; progressive neurodegeneration; reconstitution; vector

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 affect on the central nervous system (CNS), leading to progressive neurodegeneration and premature death. Currently, several treatments are available to manage these diseases but no treatments exist that can delay or prevent neurodegeneration in the CNS. Therefore, the overall goal of this project is to exploit stem cells derived from bone marrow, referred to as mesenchymal stem cells (MSCs), as cellular vectors to reconstitute deficient enzyme activity in the brain as a means to delay and/or prevent neurodegeneration. Herein, MSCs are injected directly into the CNS of non-human primate (Rhesus macaques) infants and their overall engraftment levels and anatomic distribution in brain are quantified. These data are then 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 also be closely monitored to look for signs of rejection of the transplanted cells. Once the safety of the approach is established, the MSCs are transplanted into infant macaques afflicted with Krabbe disease, a form of storage disease that effects the nervous system, and their effect on disease progression is evaluated. By employing a relevant large animal model, data obtained from these studies will aide in developing more efficacious therapies for treating human infants afflicted with lysosomal storage disease that involved the CNS.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 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。 目前，有几种治疗方法可用于治疗这些疾病，但尚无可以延迟或预防中枢神经系统神经退行性变的治疗方法。 因此，该项目的总体目标是利用骨髓干细胞（称为间充质干细胞（MSC））作为细胞载体来重建大脑中缺陷的酶活性，作为延迟和/或预防神经退行性变的手段。 在此，将间充质干细胞直接注射到非人类灵长类动物（恒河猴）婴儿的中枢神经系统中，并对它们在大脑中的整体植入水平和解剖分布进行量化。 然后将这些数据与对动物健康、发育、行为和运动技能的影响相关联，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，因此还将密切监测每个移植受者的免疫状态，以寻找移植细胞排斥的迹象。 一旦确定该方法的安全性，就会将间充质干细胞移植到患有克拉伯病（一种影响神经系统的贮积病）的幼年猕猴中，并评估它们对疾病进展的影响。 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疗法来治疗患有涉及中枢神经系统的溶酶体贮积病的人类婴儿。