Cell Transplantation and Gene Therapy Institute, The Third Xiang Ya Hospital, Central South University, Changsha, Hunan, China.
Engineering and Technology Research Center for Xenotransplantation of Hunan Province, Changsha, China.
Xenotransplantation. 2018 Sep;25(5):e12405. doi: 10.1111/xen.12405. Epub 2018 Jun 22.
Hypoxia-induced damage is one of the key factors associated with islet graft dysfunction. Mesenchymal stem cells (MSCs) could be used to enhance the therapeutic effect of islet transplantation due to their paracrine potential such as exosomes. In this study, we investigated whether exosomes from human umbilical cord-derived MSC-conditioned medium (hu-MSC-CM) could increase the survival and function of neonatal porcine islet cell clusters (NICCs) exposed to hypoxia.
Neonatal porcine islet cell clusters were cultured with hu-MSC-CM, with or without exosomes, and native medium RPMI-1640 (Control) under hypoxic conditions (1% O ). The effects of exosomes on NICCs viability and function in vitro were examined by FACS, the Loops system, and the Extracellular Flux assay, respectively.
Compared with NICCs cultured in RPMI-1640 medium and hu-MSC-CM without exosomes, the survival ratio, viability, and function increased in NICCs cultured in hu-MSC-CM with exosomes.
This study found that hu-MSC-CM could protect NICCs from hypoxia-induced dysfunction, and exosomes played an important role in hypoxic resistance, suggesting a potential strategy to improve islet transplantation outcomes.
缺氧诱导损伤是与胰岛移植物功能障碍相关的关键因素之一。间充质干细胞(MSCs)由于其旁分泌潜能,如外泌体,可用于增强胰岛移植的治疗效果。在这项研究中,我们研究了人脐带间充质干细胞条件培养基(hu-MSC-CM)中的外泌体是否可以增加暴露于缺氧环境下的新生猪胰岛细胞簇(NICCs)的存活和功能。
将新生猪胰岛细胞簇在 hu-MSC-CM 中培养,有或没有外泌体,并在缺氧条件下(1% O )在 RPMI-1640 培养基(对照)中培养。通过 FACS、Loops 系统和细胞外通量测定分别检测外泌体对 NICCs 体外活力和功能的影响。
与在 RPMI-1640 培养基和无外泌体的 hu-MSC-CM 中培养的 NICCs 相比,在含有外泌体的 hu-MSC-CM 中培养的 NICCs 的存活率、活力和功能均增加。
本研究发现 hu-MSC-CM 可保护 NICCs 免受缺氧诱导的功能障碍,外泌体在缺氧抵抗中发挥重要作用,提示改善胰岛移植结果的潜在策略。