Immunologic consequences of multiple, high-dose administration of allogeneic mesenchymal stem cells to baboons
Immunologic consequences of multiple, high-dose administration of allogeneic mesenchymal stem cells to baboons
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DOI：
10.3727/000000006783981503
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发表时间：
2006-01-01
影响因子：
3.3
通讯作者：
McIntosh, Kevin R.
中科院分区：
文献类型：
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作者：
Beggs, Kirstin J.;Lyubimov, Alex;McIntosh, Kevin R.
间充质干细胞（MSC）表达低免疫原性，并在体外表现出免疫调节特性，可以安全地将其移植到不相关的免疫功能正常的受体中，而无需使用药物免疫抑制。为了检验这一假设，对三组狒狒（每组三只动物）进行了如下注射：第 1 组动物注射媒介物；第2组动物静脉注射DiI标记的MSCs（5 x 10(6) MSCs/kg体重），6周后肌内注射来自同一供体的DiO标记的MSCs（5 x 10(6) MSCs/kg）；第3组动物的治疗与第2组类似，只是MSC来自两个不同的供体。第二次注射 MSC 4 周后进行的肌肉活检显示，50% 的接受者体内持续存在 DiO 标记的 MSC。每隔一定时间抽血以评估基本免疫参数（Con A 丝裂原反应性、PBMC 表型、免疫球蛋白水平），并确定 T 细胞和同种抗体对供体同种抗原的反应。大多数受者的宿主 T 细胞对供体同种抗原的反应降低，但不会抑制 T 细胞对 Con A 的整体反应，或影响免疫系统的基本参数。所有受体狒狒都会产生与供体 PBMC 发生反应的同种抗体。六只动物中有两只产生了与间充质干细胞反应的同种抗体。我们得出的结论是，多次施用高剂量的同种异体间充质干细胞会影响同种异体免疫反应，但不会损害受体狒狒的整体免疫系统。诱导宿主 T 细胞对供体同种异体抗原的低反应性可能有利于 MSC 的存活。
Mesenchymal stem cells (MSCs) express low immunogenicity and demonstrate immunomodulatory properties in vitro that may safely allow their transplantation into unrelated immunocompetent recipients without the use of pharmacologic immunosuppression. To test this hypothesis, three groups of baboons (three animals per group) were injected as follows: group 1 animals were injected with vehicle; group 2 animals were injected IV with DiI-labeled MSCs (5 x 10(6) MSCs/kg body weight) followed 6 weeks later by IM injections of DiO-labeled MSCs (5 x 10(6) MSCs/kg) from the same donor; and group 3 animals were treated similarly as group 2 except that MSCs were derived from two different donors. Muscle biopsies, performed 4 weeks after the second injection of MSCs, showed persistence of DiO-labeled MSCs in 50% of the recipients. Blood was drawn at intervals for evaluation of basic immune parameters (Con A mitogen responsiveness, PBMC phenotyping, immunoglobulin levels), and to determine T-cell and alloantibody responses to donor alloantigens. Host T-cell responses to donor alloantigens were decreased in the majority of recipients without suppressing the overall T-cell response to Con A, or affecting basic parameters of the immune system. All recipient baboons produced alloantibodies that reacted with donor PBMCs. Two of six animals produced alloantibodies that reacted with MSCs. We conclude that multiple administrations of high doses of allogeneic MSCs affected alloreactive immune responses without compromising the overall immune system of recipient baboons. The induction of host T-cell hyporesponsiveness to donor alloantigens may facilitate MSC survival.