y Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Accelerate Cutaneous Wound Healing by Enhancing Angiogenesis through Delivering Angiopoietin-2
y Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Accelerate Cutaneous Wound Healing by Enhancing Angiogenesis through Delivering Angiopoietin-2
复制标题
源自人脐带间充质干细胞的外泌体通过传递 Angiopoietin-2 增强血管生成来加速皮肤伤口愈合
DOI：
10.1007/s12015-020-09992-7
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发表时间：
2020-07-02
影响因子：
4.8
通讯作者：
Yan, Yongmin
中科院分区：
文献类型：
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作者：
Liu, Jinwen;Yan, Zhixin;Yan, Yongmin
人类脐带间充质干细胞 (hucMSC) 及其外泌体 (hucMSC-Exs) 在皮肤伤口愈合中发挥重要作用，但其潜在机制仍知之甚少。通过使用深二级烧伤大鼠模型，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），并且用hucMSC-Exs治疗通过外泌体介导的Ang-2转移增强了伤口区域和人脐静脉内皮细胞（HUVEC）中Ang-2蛋白的表达。此外，hucMSC-Exs促进了HUVEC的增殖、迁移和管形成能力。此外，hucMSC-Ex 中 Ang-2 的过表达进一步增强了 HUVEC 迁移和管形成，并对大鼠皮肤伤口发挥治疗和促血管生成作用，而 hucMSC-Ex 中 Ang-2 的敲低消除了这些治疗和促血管生成作用。综上所述，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发挥重要作用，并进一步表明基于 hucMSC-Ex 的治疗可能作为促进皮肤伤口愈合的有前途的治疗方法。
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 healingin vivowere investigated. We found that hucMSC-Exs accelerated skin wound healing and angiogenesis, inducing a higher wound-closure rate and increased expression of CD31in 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.