Sustained released of microRNA-99b-3p abundant exosomes derived from adipose stem cell encapsulated with hydrogel microparticles (HMPs) for long-term osteoarthritis treatment

作者：Zhaowei Yin, Shaowei Pan, Chen Shi, Guanfu Wu, Yan Feng, Chaoren Qin, Jing Zhang, Ziyi Yu, Bin Liang, Jianchao Gui · 发表于：Research Square · 年份：2023 · DOI：10.21203/rs.3.rs-2621379/v1 · 被引用次数：1 · 研究领域：Extracellular vesicles in disease、Osteoarthritis Treatment and Mechanisms、Mesenchymal stem cell research

Abstract Adipose derived stem cells (ADSCs) have the potential to attenuate osteoarthritis (OA); however, complications such as immune rejection and tumour formation limit their application. Exosomes (Exos)-mediated acellular therapy is promising in alleviating OA. This study aims to confirm whether ADSC-exos derived from infrapatellar fat pad (IPFP, Exos IPFP ) are more suitable for ameliorating OA than ADSC-exos derived from subcutaneous fat (ScAT, Exo ScAT ) in vitro and in DMM models. Then, we investigated the regulatory mechanism by which the two kinds of Exos inhibit extracellular matrix (ECM) degradation in OA. ADSCs were successfully isolated and Exos were then obtained. Exos IPFP exhibited better attenuated effects on osteoarthritic chondrocytes in vitro and in vivo than Exo ScAT . Small RNA sequencing was performed and the results shown that miR-99b-3p was upregulated in Exos IPFP . In vitro experiments confirmed that ADAMTS4 is a direct downstream target of miR-99b-3p. Over-expression miR-99b-3p in Exos ScAT (Exos ScAT-99b-3p ) indicated that miR-99b-3p serves a positive role for OA treatment by inhibiting ADAMTS4 expression both in vitro and in vivo. In addition, hydrogel microparticles (HMPs) system was prepared by microfluidic technology, and confirmed the beneficial results for long-term therapeutic by continuous release of Exos. Take together, these results suggest that the therapeutic effects of ADSC-Exos may vary according to differential expression of miRNA...