Stem cell–derived extracellular vesicles (EVs) offer alternative approaches to stem cell–based therapy for regenerative medicine. In this study, stem cell EVs derived during differentiation are developed to use as cell-free therapeutic systems by inducing tissue-specific differentiation. EVs are isolated from human adipose-derived stem cells (HASCs) during white and beige adipogenic differentiation (D-EV and BD-EV, respectively) via tangential flow filtration. D-EV and BD-EV can successfully differentiate HASCs into white and beige adipocytes, respectively. D-EV are transplanted with collagen/methylcellulose hydrogels on the backs of BALB/c mice, and they produce numerous lipid droplets in injected sites. Treatments of BD-EV attenuate diet-induced obesity through browning of adipose tissue in mice. Furthermore, high-fat diet–induced hepatic steatosis and glucose tolerance are improved by BD-EV treatment. miRNAs are responsible for the observed effects of BD-EV. These results reveal that secreted EVs during stem cell differentiation into white adipocytes or beige adipocytes can promote cell reprogramming.

干细胞衍生的细胞外囊泡（EV）为基于干细胞的再生医学治疗提供了替代方法。在这项研究中，通过诱导组织特异性分化，将分化过程中衍生的干细胞电动汽车开发为无细胞治疗系统。通过切向流过滤，在白色和米色成脂分化（分别为D-EV和BD-EV）过程中，从人类脂肪干细胞（HASC）中分离出EV。D-EV和BD-EV可以分别成功地将HASC分化为白色和米色脂肪细胞。D-EV在BALB / c小鼠的背部移植了胶原蛋白/甲基纤维素水凝胶，并在注射部位产生大量脂滴。BD-EV的治疗通过使小鼠脂肪组织褐变来减轻饮食引起的肥胖。此外，BD-EV治疗可改善高脂饮食诱导的肝脂肪变性和葡萄糖耐量。miRNA负责观察到的BD-EV效应。这些结果表明，在干细胞分化为白色脂肪细胞或米色脂肪细胞的过程中分泌的EV可以促进细胞重编程。