Donor‐derived adipose‐derived mesenchymal stem cells (ADMSCs) dampen the alloimmune response and exosomes are reported to have biological activity similar to their parent cells. Here, we investigated the roles of exosomes from donor‐derived ADMSCs (ADMSC‐exo) in vascularized composite allotransplantation (VCA). Brown Norway‐to‐Lewis rat hindlimb transplantations were intravenously treated with either exosome from donor‐derived ADMSCs or phosphate‐buffered saline, combined with a short course of immunosuppression. We established that the treatment with ADMSC‐exo prolongs the survival time of VCA grafts. Skin and muscle samples from ADMSC‐exo‐treated animals showed no histological signs of rejection, but samples from controls showed rejection of degree III. Comparing to the control group, a significant increase of donor cell chimerism, Tr1 and Treg, while a decrease of CD4⁺ T and Th1 cells were observed in the ADMSC‐exo‐treated group. Our findings imply that ADMSC‐exo may be a valuable and safe treatment for extending VCA graft survival.

中文翻译：

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来自供体脂肪间充质干细胞的外泌体延长血管化复合同种异体移植物的存活

供体来源的脂肪来源间充质干细胞（ADMSCs）抑制同种免疫反应，据报道外泌体具有与其亲本细胞相似的生物活性。在这里，我们研究了来自供体来源的 ADMSCs (ADMSC-exo) 的外泌体在血管化复合同种异体移植 (VCA) 中的作用。Brown norway-to-Lewis 大鼠后肢移植用来自供体来源的 ADMSCs 的外泌体或磷酸盐缓冲盐水进行静脉内治疗，并结合短期免疫抑制治疗。我们确定 ADMSC-exo 治疗延长了 VCA 移植物的存活时间。来自 ADMSC 外源治疗动物的皮肤和肌肉样本没有显示出排斥的组织学迹象，但来自对照的样本显示出 III 级排斥。与对照组相比，供体细胞嵌合体Tr1和Treg显着增加，在 ADMSC 外处理组中观察到⁺ T 和 Th1 细胞。我们的研究结果表明，ADMSC-exo 可能是延长 VCA 移植物存活率的一种有价值且安全的治疗方法。