Center for Research and Innovation, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand.
Department of Orthopaedics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
FEBS Open Bio. 2022 Feb;12(2):470-479. doi: 10.1002/2211-5463.13352. Epub 2021 Dec 24.
Mesenchymal stem cells (MSCs) have been proposed to have potential for tissue engineering and cell therapy due to their multilineage differentiation potential and ability to secrete numerous paracrine factors, including extracellular vesicles (EVs). Increasing evidence has demonstrated that MSC-derived EVs (MSC-EVs) are able to induce the repair of tissue damage and regulate the immune system. However, their role in cancer development is still unclear. Reports have suggested that whether MSC-EVs have an inhibitory or promoting effect on cancer is dependent on the type of cancer. In this study, the role of MSC-EVs in the regulation of leukemic cell growth in vitro was investigated. The EVs were collected from conditioned media of MSCs by ultrafiltration using a 10 kDa molecular weight cutoff (MWCO) filter. The isolated MSC-EVs were comprised of microvesicles and exosomes, as examined by the size of vesicles and exosomal proteins, CD81 and flotillin-1. Cell proliferation, cell cycle status, apoptosis, and gene expression were examined in the leukemic cell lines NB4 and K562 after treatment with MSC-EVs. Suppression of cell proliferation and induction of apoptosis was observed. Gene expression analysis revealed differential expression of apoptotic-related genes in NB4 and K562. MSC-EVs increased the expression of BID and BAX and decreased expression of BCL2, indicating the induction of intrinsic apoptosis in NB4. In contrast, MSC-EVs increased the expression of the death receptor gene TRAILR2 and cell cycle regulator genes P21 and CCNE2 in K562. In conclusion, MSC-EVs partially induce leukemic cell apoptosis, and thus may have potential for the development of supportive therapies for leukemia.
间充质干细胞（MSCs）由于其多能性分化潜力和分泌大量旁分泌因子的能力，包括细胞外囊泡（EVs），被认为具有组织工程和细胞治疗的潜力。越来越多的证据表明，MSC 来源的 EVs（MSC-EVs）能够诱导组织损伤修复和调节免疫系统。然而，它们在癌症发展中的作用尚不清楚。有报道称，MSC-EVs 是否对癌症有抑制或促进作用取决于癌症的类型。在这项研究中，研究了 MSC-EVs 在体外调节白血病细胞生长中的作用。通过使用 10 kDa 分子量截止（MWCO）过滤器进行超滤，从 MSC 条件培养基中收集 EVs。通过囊泡和外泌体蛋白 CD81 和 flotillin-1 的大小，鉴定分离的 MSC-EVs 由微泡和外泌体组成。用 MSC-EVs 处理 NB4 和 K562 白血病细胞系后，检测细胞增殖、细胞周期状态、凋亡和基因表达。观察到细胞增殖受到抑制和凋亡诱导。基因表达分析显示 NB4 和 K562 中凋亡相关基因的表达存在差异。MSC-EVs 增加了 BID 和 BAX 的表达，降低了 BCL2 的表达，表明 NB4 中诱导了内在凋亡。相反，MSC-EVs 增加了 K562 中死亡受体基因 TRAILR2 和细胞周期调节基因 P21 和 CCNE2 的表达。总之，MSC-EVs 部分诱导白血病细胞凋亡，因此可能具有开发白血病支持性治疗的潜力。
