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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此，可以在其他清晰的条目中表示。列出的机构是 对于中心，这不一定是调查员的机构。 溶酶体储存疾病是一组异质性疾病，其特征是几种酶之一的遗传缺陷，这对于体内许多器官中的代谢产物分解所必需。 在某些情况下，酶缺乏对中枢神经系统（CNS）产生了深远的影响，从而导致进行性神经退行性和过早死亡。 当前，有几种治疗方法可用于管理这些疾病，但没有治疗可以延迟或阻止中枢神经系统中神经退行性的治疗方法。 因此，该项目的总体目标是利用源自骨髓的干细胞，称为间充质干细胞（MSC），作为细胞向量，以重新构成大脑中缺乏酶活性，以作为延迟和/或预防神经变性的手段。 在此，将MSC直接注入非人类灵长类动物（恒河猕猴）婴儿的中枢神经中心及其整体植入水平和大脑中的解剖分布。 然后，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，MSC是从无关的供体中得出的，因此每个移植受体的免疫状态也将受到密切监测，以寻找拒绝移植细胞的迹象。 一旦确定了该方法的安全性，MSC就会将其移植到患有Krabbe疾病的婴儿猕猴中，这是一种影响神经系统的储存疾病形式，并评估了其对疾病进展的影响。 通过采用相关的大型动物模型，从这些研究获得的数据将有助于开发更有效的疗法，以治疗患有CNS的溶酶体储存疾病的人。