Hubei Key Laboratory of Medical Technology on Transplantation, Transplant Center of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
Transplantation Center of the Third Xiangya Hospital of Central South University, Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, Changsha, China.
J Cell Physiol. 2021 Aug;236(8):5895-5905. doi: 10.1002/jcp.30274. Epub 2021 Jan 16.
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.
供体来源的脂肪来源间充质干细胞（ADMSCs）可抑制同种免疫反应，并且已有报道称外泌体具有与其亲本细胞相似的生物学活性。在这里，我们研究了供体来源的 ADMSC（ADMSC-exo）外泌体在血管化复合组织同种异体移植（VCA）中的作用。通过静脉内给予布朗-挪威大鼠到刘易斯大鼠的后肢移植物，用来自供体来源的 ADMSC 的外泌体或磷酸盐缓冲盐水处理，同时进行短期免疫抑制治疗。我们确定了 ADMSC-exo 的治疗可延长 VCA 移植物的存活时间。来自 ADMSC-exo 治疗动物的皮肤和肌肉样本没有排斥反应的组织学迹象，但对照样本显示出 III 级排斥反应。与对照组相比，ADMSC-exo 治疗组中观察到供体细胞嵌合、Tr1 和 Treg 的显著增加，而 CD4 T 和 Th1 细胞的减少。我们的研究结果表明，ADMSC-exo 可能是一种有价值且安全的治疗方法，可延长 VCA 移植物的存活时间。
