SAFETY OF MESENCHYMAL STEM CELL ADMINISTRATION TO THE CNS OF RHESUS MACAQUES

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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.