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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 最近的研究表明，间充质干细胞(MSCs)具有强大的免疫调节活性，但在同种异体移植环境中，这些细胞是否能逃避免疫监视仍存在争议。我们评价了接受纹状体内注射低剂量(LD)和高剂量(HD)雄性MSCs的雌性幼年恒河猴的免疫状态。移植后10天，所有移植动物的循环白细胞和淋巴细胞数量均较术前有短暂但显著的增加，其中HD受体的最大差异为1.5倍。因此，流式细胞仪分析证实循环中CD8+ve、CD16+ve、CD28+ve和CD8+ve/CD16+ve亚群水平升高。供体MSCs与HD移植受者的PBMNCs共培养，而非LD或SHAMS的PBMNCs在连续两倍稀释液中显示出细胞毒作用，最大值分别为30.64%和15.12%。基于FACS的6个MSC受者的血清或血浆筛查在所有样本中检测到FBS特异性抗体，而基于ELISA法在1个LD和1个HD受者中检测到MHC I类特异性抗体，表明单倍型错配依赖效应。这些数据表明，同种异体骨髓间充质干细胞直接注射到中枢神经系统中，以细胞剂量依赖的方式在外周血液中诱导可检测到的免疫反应。