Jeong S-H, Ji Y-H, Yoon E-S
Department of Plastic Surgery, Korea University Guro Hospital, Seoul, Korea.
Department of Plastic Surgery, Korea University Anam Hospital, Seoul, Korea.
Transplant Proc. 2014 Jun;46(5):1606-14. doi: 10.1016/j.transproceed.2013.12.069.
Many reports have shown that bone marrow-derived mesenchymal stem cells exhibit immunosuppressive effects in allogeneic transplantation. However, few reports have evaluated the immunosuppressive properties of adipose tissue-derived mesenchymal stem cells (ASCs) in vitro and in vivo. In this study, we investigated the immunosuppressive characteristics of ASCs, and investigated whether ASCs originating from donor rats prolong allotransplant survival in a rat hind limb allotransplantation model. T-cell proliferation stimulated by allogeneic stimuli or mitogen with or without ASCs originating from the donor was assessed in vitro. The effects of cellular contact or soluble factors on the inhibition of T-cell proliferation were also evaluated. In the in vivo study, cultured ASCs (1 × 10(5)) that originated from the donor were injected into recipient animals intravenously immediately after operation, followed by 1 dose per day for 3 consecutive days post-transplantation. When immune rejection occurred, the survival time of allotransplants was determined and rejected tissue was histologically and immunochemically assessed for determining regulatory T-cell infiltration. ASCs inhibited the T-cell proliferation stimulated by alloantigen or mitogen in a dose-dependent manner, and recipient T cells proliferated less in animals treated with ASCs than in controls. Although ASCs were separated from T cells, ASCs persisted to elicit a suppressive effect. ASC culture supernatants did not inhibit T-cell proliferation; however, supernatants obtained from the mixed lymphocyte reaction in the presence of ASCs suppressed T-cell proliferation. ASCs prolonged allotransplant survival time, reduced inflammatory cell infiltration, and induced regulatory T cells. In conclusion, ASCs can exhibit in vitro immunosuppressive properties and prolong allotransplant survival time in a rat hind limb composite tissue allotransplantation model, possibly through the induction of regulatory T cells.
许多报告显示，骨髓间充质干细胞在同种异体移植中表现出免疫抑制作用。然而，很少有报告评估脂肪组织来源的间充质干细胞（ASC）在体外和体内的免疫抑制特性。在本研究中，我们调查了ASC的免疫抑制特征，并研究了源自供体大鼠的ASC是否能延长大鼠后肢同种异体移植模型中的同种异体移植存活时间。在体外评估了在有或没有源自供体的ASC的情况下，同种异体刺激物或有丝分裂原刺激的T细胞增殖。还评估了细胞接触或可溶性因子对T细胞增殖抑制的影响。在体内研究中，将源自供体的培养ASC（1×10⁵）在手术后立即静脉注射到受体动物体内，然后在移植后连续3天每天注射1剂。当发生免疫排斥时，确定同种异体移植的存活时间，并对排斥组织进行组织学和免疫化学评估以确定调节性T细胞浸润情况。ASC以剂量依赖性方式抑制同种异体抗原或有丝分裂原刺激的T细胞增殖，并且在用ASC处理的动物中受体T细胞的增殖比对照组少。尽管ASC与T细胞分离，但ASC仍持续发挥抑制作用。ASC培养上清液不抑制T细胞增殖；然而，在ASC存在下从混合淋巴细胞反应中获得的上清液抑制T细胞增殖。ASC延长了同种异体移植的存活时间，减少了炎性细胞浸润，并诱导了调节性T细胞。总之，在大鼠后肢复合组织同种异体移植模型中，ASC可能通过诱导调节性T细胞而表现出体外免疫抑制特性并延长同种异体移植的存活时间。
