The underlying mechanisms of human umbilical cord mesenchymal stem cells (hucMSCs) and their exosomes (hucMSC-Exs), which play significant roles in skin wound healing, remain poorly understood. By using a rat model of deep second-degree burn injury, the roles of hucMSC-Exs in angiogenesis and cutaneous wound healing in vivo were investigated. We found that hucMSC-Exs accelerated skin wound healing and angiogenesis, inducing a higher wound-closure rate and increased expression of CD31 in vivo. We also discovered that hucMSC-Exs contained angiopoietin-2 (Ang-2), and treatment with hucMSC-Exs enhanced the expression of the Ang-2 protein in the wound area and human umbilical vein endothelial cells (HUVECs) through exosomal-mediated Ang-2 transfer. Moreover, hucMSC-Exs promoted the proliferative, migratory, and tube-forming ability of HUVECs. Furthermore, overexpression of Ang-2 in hucMSC-Exs further enhanced HUVEC migration and tube formation and exerted therapeutic and proangiogenic effects in cutaneous wounds in rats, whereas knockdown of Ang-2 in hucMSC-Exs abrogated these therapeutic and proangiogenic effects. Taken together, our results indicated that hucMSC-Ex-derived Ang-2 plays a significant role in tube formation of HUVECs and promotion of angiogenesis, and further suggested that hucMSC-Ex-based therapy may serve as a promising therapeutic approach for promoting cutaneous wound healing.

人类脐带间充质干细胞 (hucMSCs) 及其外泌体 (hucMSC-Exs) 在皮肤伤口愈合中起重要作用的潜在机制仍然知之甚少。通过使用深二度烧伤大鼠模型，研究了hucMSC-Exs在体内血管生成和皮肤伤口愈合中的作用。我们发现 hucMSC-Exs 加速皮肤伤口愈合和血管生成，诱导更高的伤口闭合率并增加体内 CD31 的表达。我们还发现，hucMSC-Exs 含有血管生成素-2 (Ang-2)，hucMSC-Exs 治疗通过外泌体介导的 Ang 增强伤口区域和人脐静脉内皮细胞 (HUVECs) 中 Ang-2 蛋白的表达-2 转移。此外，hucMSC-Exs 促进了 HUVECs 的增殖、迁移和成管能力。此外，在 hucMSC-Exs 中过表达 Ang-2 进一步增强了 HUVEC 迁移和管形成，并在大鼠皮肤伤口中发挥治疗和促血管生成作用，而在 hucMSC-Exs 中敲低 Ang-2 消除了这些治疗和促血管生成作用。总之，我们的结果表明，hucMSC-Ex衍生的Ang-2在HUVEC的管形成和促进血管生成中起重要作用，