Cell-dose-dependent increases in circulating levels of immune effector cells in rhesus macaques following intracranial injection of allogeneic MSCs.
Cell-dose-dependent increases in circulating levels of immune effector cells in rhesus macaques following intracranial injection of allogeneic MSCs.
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DOI：
10.1016/j.exphem.2010.06.011
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发表时间：
2010-10
影响因子：
2.6
通讯作者：
Phinney, Donald G.
中科院分区：
文献类型：
--
作者：
Isakova, Iryna A.;Dufour, Jason;Lanclos, Calvin;Bruhn, Julie;Phinney, Donald G.
间充质干细胞（MSC）具有强大的免疫调节活性，但它们是否能在同种异体移植环境中逃避免疫监视仍存在争议。在此，我们评估是否管理的主要组织相容性（MHC）I类不匹配的骨髓间充质干细胞诱导恒河猴的免疫反应。将来自雄性供体的MSC以两种不同剂量颅内注射到八只免疫活性的雌性婴儿恒河猴中。在手术前和手术后10、30和90-180天通过流式细胞术定量血细胞计数和淋巴细胞亚群的循环水平。受体PBMNCs对供体MSCs的免疫反应性在体外进行了评价，同种抗体在体内的产生通过ELISA和流式细胞术进行了测定。在大多数移植受者中，MSC移植诱导了循环白色血细胞、淋巴细胞和中性粒细胞的短暂但显着的增加，但假手术对照动物却没有。流式细胞术分析显示，CD 8 +ve，CD 16 +ve，CD 8 +ve/CD 16 +ve淋巴细胞亚群在外周血中，管理的MSC剂量，和供体和受体之间的抗原错配程度的扩增之间的强相关性。在几个移植受者中也检测到MSC特异性同种抗体。然而，从手术后的移植受体收获的PBMNCs在体外再激发时对供体MSC没有表现出裂解活性。骨髓间充质干细胞诱导恒河猴的同种异体移植反应，主要涉及CD 8 +ve，CD 16 +ve，和CD 8 +ve/CD 16 +ve淋巴细胞亚群，是细胞剂量和单倍型依赖性。这项研究表明，骨髓间充质干细胞是弱免疫原性的体内移植时，跨MHC I类障碍。
Mesenchymal stem cells (MSCs) possess potent immuno-modulatory activity but whether they evade immune surveillance in an allogeneic transplant setting remains controversial. Herein we evaluated whether administration of major histocompatibility (MHC) class I mismatched MSCs induce an immune response in rhesus macaques. MSCs from a male donor were injected intra-cranially at two different doses into eight immuno-competent female infant rhesus macaques. Blood cell counts and circulating levels of lymphocyte subpopulations were quantified prior to surgery and at 10, 30, and 90–180 days post-surgery by flow cytometry. Immuno-reactivity of recipient PBMNCs to donor MSCs was evaluated in vitro and allo-antibody production in vivo was determined by ELISA and flow cytometry. MSC transplantation induced transient but significant increases in circulating white blood cells, lymphocytes, and neutrophils in most transplant recipients but not sham-operated control animals. Flow cytometric analysis revealed a strong correlation between expansion of CD8+ve, CD16+ve, and CD8+ve/CD16+ve lymphocyte subpopulations in peripheral blood, the dose of administered MSCs, and degree of antigenic mismatch between donor and recipient. MSC-specific allo-antibodies were also detected in several transplant recipients. However, PBMNCs harvested from transplant recipients post-surgery exhibited no lytic activity against donor MSCs in vitro upon re-challenge. MSCs induced an allo-graft response in rhesus macaques that involved principally CD8+ve, CD16+ve, and CD8+ve/CD16+ve lymphocyte subpopulations and was cell dose and haplotype dependent. This study demonstrates that MSCs are weakly immunogenic in vivo when transplanted across MHC class I barriers.
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