背景:脂肪组织来源的干细胞来源的凋亡体(ADSC-AB)显示出免疫调节和再生的巨大潜力,特别是在糖尿病伤口治疗中。然而,它们在当地的应用受到监管机制不明确的限制,快速清除,组织保留时间短。
方法:我们通过mRNA测序和microRNA(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节途径,然后通过基因敲除进行验证。为了防止快速清除,我们采用微流体技术制备了甲基丙烯酸酯-酸酐明胶(GelMA)微球(GMS),用于控制ABs的释放。最后,我们评估了糖尿病大鼠伤口模型中载有ADSC-AB的GMSs(ABs@GMSs)的有效性。
结果:我们的结果表明,ADSC-ABs通过Janus激酶(JAK)-信号转导和转录激活因子(STAT)途径有效地平衡了巨噬细胞的炎症极化,由miR-20a-5p介导。此外,我们表明AB@GMS具有良好的生物相容性,明显延迟了ABs的局部清除,改善糖尿病伤口炎症并促进血管形成,从而促进其愈合。
结论:我们的研究揭示了ADSC-ABs在平衡巨噬细胞炎症极化中的调节机制,并强调了GMS延迟其局部清除的重要性。这些发现对糖尿病伤口愈合的新疗法的开发具有重要意义。
背景:这项研究得到了中国国家重点研究发展计划(2020YFA0908200)的支持,国家自然科学基金(82272263,82002053,32000937,82202467),上海市“医学人才新星”青年发展计划(22MC1940300),上海市卫生健康委员会(20204Y0354),和上海市科技发展基金(22YF1421400)。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
BACKGROUND: 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).