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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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，但细胞是否逃避同种异体移植设置的免疫监视仍然存在争议。 我们评估了接受低（LD）或高（HD）剂量雄性MSC纹状体内注射的雌性婴儿恒河猴的免疫状态。在所有移植动物中，与手术前水平相比，移植后10天观察到循环白色血细胞和淋巴细胞数量短暂但显著增加，HD受体中差异最大为1.5倍。 因此，流式细胞术分析证实了响应于MSC的HD的循环CD 8 +ve、CD 16 +ve、CD 28 +ve和CD 8 +ve/CD 16 +ve亚群的水平升高。此外，供体MSC与来自HD移植受体而不是来自LD或假手术的PBMNCs的共培养在两个连续稀释度下显示细胞毒性效应，最大值分别为30.64%和15.12%。 基于流式细胞术的筛选血清或血浆中的6个MSC受体检测FBS特异性抗体在所有样品中，而基于ELISA的测定检测到MHC I类特异性抗体在一个LD和一个HD受体，表明单倍型错配依赖的效果。这些数据表明，直接注射到CNS中的同种异体MSC以细胞剂量依赖性方式诱导可检测的外周血免疫应答。