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: 8172929
• 负责人: Donald G Phinney
• 金额: $ 6.18万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 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/8172929
• 关键词: Allogenic; Animals; Antibodies; Biological Assay; Cells; Coculture Techniques; Computer Retrieval of Information on Scientific Projects Database; Corpus striatum structure; Data; Dose; Female; Funding; Grant; Haplotypes; Immune response; Immunologic Surveillance; Infant; Injection of therapeutic agent; Institution; Leukocytes; Lymphocyte; MHC Class I Genes; Macaca mulatta; Mesenchymal Stem Cells; Operative Surgical Procedures; Plasma; Research; Research Personnel; Resources; Safety; Sampling; Screening procedure; Serum; Source; Toxic effect; Transplant Recipients; Transplantation; United States National Institutes of Health; base; immunological status; male; peripheral blood; response

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. Recent studies indicate that mesenchymal stem cells (MSCs) possess potent immuno-modulatory activity but whether the cells evade immune surveillance in an allogeneic transplant setting remains controversial. We evaluated the immunological status of female infant rhesus macaques who received intra-striatal injections of low (LD) or high (HD) dose of male MSCs. Transient but significant increases in numbers of circulating white blood cells and lymphocytes were observed 10 days post-transplantation compared to the pre-surgical levels in all transplanted animals with maximal 1.5 fold difference in HD recipients. Consequently, flow cytometric analysis confirmed elevated levels of circulating CD8+ve, CD16+ve, CD28+ve, and CD8+ve/CD16+ve subpopulations in response to the HD of MSCs. Additionally, co-culture of donor MSCs with PBMNCs obtained from HD transplant recipients but not from LD or shams showed cyto-toxic effect at two consecutive dilutions with maximal values 30.64% and 15.12% respectively. FACS-based screening of sera or plasma of six MSC recipients detected FBS-specific antibody in all samples while an ELISA-based assay detected MHC class I-specific antibodies in one LD and one HD recipients suggesting a haplotype mismatch-dependent effect. These data indicate that allogeneic MSCs injected directly into the CNS induce a detectible in peripheral blood immune response in a cell dose-dependent manner.

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。 最近的研究表明，间充质干细胞（MSC）具有有效的免疫调节活性，但细胞是否在同种异体移植环境中逃避免疫监视仍存在争议。 我们评估了接受纹状体内注射低 (LD) 或高 (HD) 剂量雄性 MSC 的雌性恒河猴幼崽的免​​疫状态。移植后 10 天，与所有移植动物的手术前水平相比，观察到循环白细胞和淋巴细胞数量出现短暂但显着的增加，HD 受者的最大差异为 1.5 倍。 因此，流式细胞术分析证实循环 CD8+ve、CD16+ve、CD28+ve 和 CD8+ve/CD16+ve 亚群水平升高，以响应 MSC 的 HD。此外，供体 MSC 与从 HD 移植受者获得的 PBMNC（而非从 LD 或假手术获得的 PBMNC）共培养在两个连续稀释度下显示出细胞毒性作用，最大值分别为 30.64% 和 15.12%。 对 6 名 MSC 接受者的血清或血浆进行基于 FACS 的筛查，在所有样本中检测到 FBS 特异性抗体，而基于 ELISA 的检测在 1 名 LD 和 1 名 HD 接受者中检测到 MHC I 类特异性抗体，表明存在单倍型错配依赖性效应。这些数据表明，直接注射到中枢神经系统的同种异体间充质干细胞以细胞剂量依赖性方式诱导外周血免疫反应。