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利用分化干细胞的细胞外囊泡将细胞重编程为白色/米色脂肪细胞。

Cell reprogramming using extracellular vesicles from differentiating stem cells into white/beige adipocytes.

机构信息

Department of Materials Science and Chemical Engineering, Hanyang University ERICA, Ansan 15588, Republic of Korea.

ExoStemTech Inc., Ansan 15588, Republic of Korea.

出版信息

Sci Adv. 2020 Mar 25;6(13):eaay6721. doi: 10.1126/sciadv.aay6721. eCollection 2020 Mar.

DOI:10.1126/sciadv.aay6721
PMID:32232152
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7096171/
Abstract

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.

摘要

干细胞衍生的细胞外囊泡 (EVs) 为再生医学中的基于干细胞的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，从分化过程中衍生的干细胞 EV 被开发为无细胞治疗系统。通过切向流过滤从人脂肪来源干细胞 (HASCs) 中分离出白色和米色成脂分化过程中的 EV (D-EV 和 BD-EV)。D-EV 和 BD-EV 可分别成功地将 HASCs 分化为白色和米色脂肪细胞。D-EV 与胶原/甲基纤维素水凝胶一起移植到 BALB/c 小鼠背部，在注射部位产生大量脂滴。BD-EV 处理可通过脂肪组织的褐色化减轻饮食诱导的肥胖。此外，BD-EV 处理可改善高脂肪饮食诱导的肝脂肪变性和葡萄糖耐量。miRNA 是 BD-EV 观察到的作用的原因。这些结果表明，干细胞分化为白色脂肪细胞或米色脂肪细胞过程中分泌的 EV 可促进细胞重编程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d55/7096171/491928bd2ce0/aay6721-F6.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d55/7096171/4af4cc8651e9/aay6721-F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d55/7096171/bdfea1356ec1/aay6721-F5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d55/7096171/491928bd2ce0/aay6721-F6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d55/7096171/5621c1e6a866/aay6721-F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d55/7096171/0120c857af0d/aay6721-F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d55/7096171/f8ca9779fede/aay6721-F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d55/7096171/4af4cc8651e9/aay6721-F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d55/7096171/bdfea1356ec1/aay6721-F5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d55/7096171/491928bd2ce0/aay6721-F6.jpg

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