miR-23a-3p-abundant small extracellular vesicles released from Gelma/nanoclay hydrogel for cartilage regeneration
miR-23a-3p-abundant small extracellular vesicles released from Gelma/nanoclay hydrogel for cartilage regeneration
复制标题
Gelma/纳米粘土水凝胶释放出丰富的 miR-23a-3p 外泌体，用于软骨再生。
DOI：
10.1080/20013078.2020.1778883
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发表时间：
2020-01-01
影响因子：
16
通讯作者：
Liu, Zhongtang
中科院分区：
文献类型：
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作者：
Hu, Hongxing;Dong, Lanlan;Liu, Zhongtang
关节软骨的自我再生能力有限，临床上对软骨缺损的治疗方法仍不尽人意。近年来的研究表明，来源于间充质干细胞的exosomes通过向受体细胞输送生物活性物质促进软骨形成，提示exosomes可能是修复软骨缺损的一种新方法。本研究旨在探讨人脐带间充质干细胞来源的小细胞外囊泡（hUC-MSCs-sEVs）对软骨再生的作用及其机制。体外实验结果表明，hUC-MSCs-sEVs可促进软骨细胞和人骨髓间充质干细胞（hBMSCs）的迁移、增殖和分化。miRNA芯片显示miR-23 a-3 p在hUC-MSCs-sEV中的表达最高。我们的数据显示，hUC-MSCs-sEVs通过转移miR-23 a-3 p来抑制PTEN的水平并提高AKT的表达，从而促进软骨再生。此外，我们还制备了用于缓释sEV的甲基丙烯酸明胶（Gelma）/纳米粘土水凝胶（Gel-nano），其具有生物相容性并表现出优异的机械性能。体内实验结果表明，含有Gelma/nanoclay水凝胶的hUC-MSCs-sEVs（Gel-nano-sEVs）有效促进软骨再生。这些结果表明，凝胶-纳米-sEVs具有很好的促进软骨形成和修复软骨缺损的能力，也为理解hUC-MSCs-sEVs在软骨再生中的作用和机制提供了有价值的数据。
ABSTRACT Articular cartilage has limited self-regenerative capacity and the therapeutic methods for cartilage defects are still dissatisfactory in clinic. Recent studies showed that exosomes derived from mesenchymal stem cells promoted chondrogenesis by delivering bioactive substances to the recipient cells, indicating exosomes might be a novel method for repairing cartilage defect. Herein, we investigated the role and mechanism of human umbilical cord mesenchymal stem cells derived small extracellular vesicles (hUC-MSCs-sEVs) on cartilage regeneration. In vitro results showed that hUC-MSCs-sEVs promoted the migration, proliferation and differentiation of chondrocytes and human bone marrow mesenchymal stem cells (hBMSCs). MiRNA microarray showed that miR-23a-3p was the most highly expressed among the various miRNAs contained in hUC-MSCs-sEVs. Our data revealed that hUC-MSCs-sEVs promoted cartilage regeneration by transferring miR-23a-3p to suppress the level of PTEN and elevate expression of AKT. Moreover, we fabricated Gelatin methacrylate (Gelma)/nanoclay hydrogel (Gel-nano) for sustained release of sEVs, which was biocompatible and exhibited excellent mechanical property. In vivo results showed that hUC-MSCs-sEVs containing Gelma/nanoclay hydrogel (Gel-nano-sEVs) effectively promoted cartilage regeneration. These results indicated that Gel-nano-sEVs have a promising capacity to stimulate chondrogenesis and heal cartilage defects, and also provided valuable data for understanding the role and mechanism of hUC-MSCs-sEVs in cartilage regeneration.