Hao Xiaoyan, Guo Yuan, Yu Xueyuan, He Lin, He Youcheng, Shu Maoguo
Department of Plastic, Aesthetic and Maxillofacial Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta West Road, Xi'an, Shaanxi 710061, PR China.
Department of Plastic, Aesthetic and Maxillofacial Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta West Road, Xi'an, Shaanxi 710061, PR China.
Tissue Cell. 2024 Dec;91:102575. doi: 10.1016/j.tice.2024.102575. Epub 2024 Oct 1.
Exosomes from adipose-derived stem cells (ADSCs) have been demonstrated to benefit angiogenesis, wound healing, and fat grafting. Small noncoding RNAs such as microRNA (miRNA) and circular RNA play critical roles in mediating the function of ADSCs-derived exosomes. However, the underlying mechanisms have not been fully elucidated. In this study, we investigated the function and mechanism of human ADSCs-derived exosomes (hADSCs-Exo) in promoting fat graft angiogenesis and adipogenic differentiation. hADSCs-Exo were isolated and identified, and treatment with hADSCs-Exo enhanced fat graft angiogenesis and adipogenic differentiation in a mouse fat graft implantation model. We found that hADSCs-Exo overexpressed miR-671-3p and promoted human umbilical vein endothelial cell (HUVEC) proliferation, migration, and invasion. Bioinformatics analysis and luciferase reporter assay validated that TMEM127 is a direct target of miR-671-3p. Rescue experiments demonstrated that TMEM127 overexpression partially antagonized the function of hADSCs-Exo in vitro, such as suppressing HUVEC cell proliferation, migration, and invasion. Moreover, TMEM127 overexpression abrogated the function of hADSCs-Exo on fat graft angiogenesis and adipogenic differentiation. Taken together, our findings demonstrate that miR-671-3p-overexpressing exosomes from ADSC promote fat graft angiogenesis and adipogenic differentiation, which highlights the potential of targeting the ADSC-Exosomes-miR-671-3p/TMEM127 axis to improve outcome of fat graft and tissue engineering regenerative medicine.
脂肪来源干细胞(ADSCs)分泌的外泌体已被证明对血管生成、伤口愈合和脂肪移植有益。微小RNA(miRNA)和环状RNA等小非编码RNA在介导ADSCs来源外泌体的功能中起关键作用。然而,其潜在机制尚未完全阐明。在本研究中,我们探讨了人ADSCs来源外泌体(hADSCs-Exo)在促进脂肪移植血管生成和脂肪生成分化中的功能及机制。分离并鉴定了hADSCs-Exo,在小鼠脂肪移植植入模型中,用hADSCs-Exo处理可增强脂肪移植的血管生成和脂肪生成分化。我们发现hADSCs-Exo过表达miR-671-3p并促进人脐静脉内皮细胞(HUVEC)的增殖、迁移和侵袭。生物信息学分析和荧光素酶报告基因检测验证了TMEM127是miR-671-3p的直接靶点。挽救实验表明,TMEM127过表达在体外部分拮抗了hADSCs-Exo的功能,如抑制HUVEC细胞的增殖、迁移和侵袭。此外,TMEM127过表达消除了hADSCs-Exo对脂肪移植血管生成和脂肪生成分化的作用。综上所述,我们的研究结果表明,ADSC来源的过表达miR-671-3p的外泌体促进脂肪移植血管生成和脂肪生成分化,这突出了靶向ADSC-外泌体-miR-671-3p/TMEM127轴以改善脂肪移植和组织工程再生医学结果的潜力。