Mao Jiayi, Qian Shutong, Zhao Qiuyu, Zhao Binfan, Lu Bolun, Zhang Liucheng, Mao Xiyuan, Zhang Yuguang, Cui Wenguo, Sun Xiaoming
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai 200011, P.R. China.
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai 200011, P.R. China.
Med. 2024 Feb 9;5(2):148-168.e8. doi: 10.1016/j.medj.2024.01.006.
Adipose tissue-derived stem cell-derived apoptotic bodies (ADSC-ABs) have shown great potential for immunomodulation and regeneration, particularly in diabetic wound therapy. However, their local application has been limited by unclear regulatory mechanisms, rapid clearance, and short tissue retention times.
We analyzed the key role molecules and regulatory pathways of ADSC-ABs in regulating inflammatory macrophages by mRNA sequencing and microRNA (miRNA) sequencing and then verified them by gene knockdown. To prevent rapid clearance, we employed microfluidics technology to prepare methacrylate-anhydride gelatin (GelMA) microspheres (GMS) for controlled release of ABs. Finally, we evaluated the effectiveness of ADSC-AB-laden GMSs (ABs@GMSs) in a diabetic rat wound model.
Our results demonstrated that ADSC-ABs effectively balanced macrophage inflammatory polarization through the janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, mediated by miR-20a-5p. Furthermore, we showed that AB@GMSs had good biocompatibility, significantly delayed local clearance of ABs, and ameliorated diabetic wound inflammation and promoted vascularization, thus facilitating its healing.
Our study reveals the regulatory mechanism of ADSC-ABs in balancing macrophage inflammatory polarization and highlightsthe importance of delaying their local clearance by GMSs. These findings have important implications for the development of novel therapies for diabetic wound healing.
This research was supported by the National Key Research and Development Program of China (2020YFA0908200), National Natural Science Foundation of China (82272263, 82002053, 32000937, and 82202467), Shanghai "Rising Stars of Medical Talents" Youth Development Program (22MC1940300), Shanghai Municipal Health Commission (20204Y0354), and Shanghai Science and Technology Development Funds (22YF1421400).
脂肪组织来源的干细胞凋亡小体（ADSC-ABs）在免疫调节和再生方面显示出巨大潜力，尤其是在糖尿病伤口治疗中。然而，其局部应用受到调控机制不明、快速清除以及组织保留时间短的限制。
我们通过mRNA测序和微小RNA（miRNA）测序分析了ADSC-ABs在调节炎性巨噬细胞中的关键作用分子和调控途径，然后通过基因敲低进行验证。为防止快速清除，我们采用微流控技术制备甲基丙烯酸酐明胶（GelMA）微球（GMS）以实现ABs的控释。最后，我们在糖尿病大鼠伤口模型中评估了负载ADSC-ABs的GMS（ABs@GMSs）的有效性。
我们的结果表明，ADSC-ABs通过miR-20a-5p介导的 Janus激酶（JAK）-信号转导和转录激活因子（STAT）途径有效平衡巨噬细胞炎性极化。此外，我们表明AB@GMSs具有良好的生物相容性，显著延迟了ABs 的局部清除，减轻了糖尿病伤口炎症并促进了血管生成，从而促进其愈合。
我们的研究揭示了ADSC-ABs在平衡巨噬细胞炎性极化中的调控机制，并强调了通过GMSs延迟其局部清除的重要性。这些发现对糖尿病伤口愈合新疗法的开发具有重要意义。
本研究得到中国国家重点研发计划（2020YFA0908200）、国家自然科学基金（82272263、82002053、32000937和822…2467）、上海“医苑新星”青年医学人才培养资助计划（22MC1940300）、上海市卫生健康委员会（20204Y0354）以及上海市科学技术发展基金（22YF1421400）的支持。
