PMID- 32613452 OWN - NLM STAT- MEDLINE DCOM- 20220303 LR - 20220303 IS - 2629-3277 (Electronic) IS - 2629-3277 (Linking) VI - 17 IP - 2 DP - 2021 Apr TI - Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Accelerate Cutaneous Wound Healing by Enhancing Angiogenesis through Delivering Angiopoietin-2. PG - 305-317 LID - 10.1007/s12015-020-09992-7 [doi] AB - 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. FAU - Liu, Jinwen AU - Liu J AD - Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, School of Medicine, Jiangsu University, 301 Xuefu Road, 212013, Zhenjiang, Jiangsu, People's Republic of China. FAU - Yan, Zhixin AU - Yan Z AD - Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, Jiangsu, 212000, People's Republic of China. FAU - Yang, Fuji AU - Yang F AD - Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, School of Medicine, Jiangsu University, 301 Xuefu Road, 212013, Zhenjiang, Jiangsu, People's Republic of China. FAU - Huang, Yan AU - Huang Y AD - Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, School of Medicine, Jiangsu University, 301 Xuefu Road, 212013, Zhenjiang, Jiangsu, People's Republic of China. FAU - Yu, Yao AU - Yu Y AD - Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, School of Medicine, Jiangsu University, 301 Xuefu Road, 212013, Zhenjiang, Jiangsu, People's Republic of China. FAU - Zhou, Liping AU - Zhou L AD - Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, School of Medicine, Jiangsu University, 301 Xuefu Road, 212013, Zhenjiang, Jiangsu, People's Republic of China. FAU - Sun, Zixuan AU - Sun Z AD - Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, School of Medicine, Jiangsu University, 301 Xuefu Road, 212013, Zhenjiang, Jiangsu, People's Republic of China. FAU - Cui, Dawei AU - Cui D AD - Department of Blood Transfusion, The First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, China. FAU - Yan, Yongmin AU - Yan Y AD - Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, School of Medicine, Jiangsu University, 301 Xuefu Road, 212013, Zhenjiang, Jiangsu, People's Republic of China. yym@ujs.edu.cn. LA - eng PT - Journal Article PL - United States TA - Stem Cell Rev Rep JT - Stem cell reviews and reports JID - 101752767 RN - 0 (Angiogenesis Inducing Agents) RN - 0 (Angiopoietin-2) SB - IM MH - *Angiogenesis Inducing Agents MH - Angiopoietin-2/*administration & dosage/genetics MH - Animals MH - Cell Movement MH - *Exosomes MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - *Mesenchymal Stem Cells MH - Rats MH - Umbilical Cord/cytology MH - *Wound Healing OTO - NOTNLM OT - Ang-2 OT - Angiogenesis OT - Cutaneous wound healing OT - Exosomes OT - hucMSCs EDAT- 2020/07/03 06:00 MHDA- 2022/03/04 06:00 CRDT- 2020/07/03 06:00 PHST- 2020/07/03 06:00 [pubmed] PHST- 2022/03/04 06:00 [medline] PHST- 2020/07/03 06:00 [entrez] AID - 10.1007/s12015-020-09992-7 [pii] AID - 10.1007/s12015-020-09992-7 [doi] PST - ppublish SO - Stem Cell Rev Rep. 2021 Apr;17(2):305-317. doi: 10.1007/s12015-020-09992-7.