Theranostics 2018; 8(1):169-184. doi:10.7150/thno.21234

Research Paper

Exosomes from human umbilical cord blood accelerate cutaneous wound healing through miR-21-3p-mediated promotion of angiogenesis and fibroblast function

Yin Hu1,4*, Shan-Shan Rao1,5*, Zhen-Xing Wang1, Jia Cao1, Yi-Juan Tan1, Juan Luo1, Hong-Ming Li1,4, Wei-She Zhang6, Chun-Yuan Chen1✉, Hui Xie1,2,3,4,5✉

1. Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China;
2. Hunan Key Laboratory of Organ Injury, Aging and Regenerative Medicine, Changsha, Hunan, China;
3. Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China;
4. Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China;
5. Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China;
6. Department of Obstetrics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
* Yin Hu and Shan-Shan Rao contributed equally to this work.

Abstract

The application of blood plasma for soft tissue wound healing is receiving much more attention recently. Exosomes are critical paracrine mediators that can be obtained from biological fluids including plasma and be able to induce regenerative effects by transferring bioactive molecules such as microRNAs (miRNAs). This study aimed to investigate the effects of exosomes from human umbilical cord blood plasma (UCB-Exos) on wound healing and to elucidate the underlying mechanism.

Methods: UCB-Exos were isolated by ultracentrifugation and subcutaneously injected into full-thickness skin wounds in mice. The efficacy of UCB-Exos on wound healing was evaluated by measuring wound closure rates, histological analysis and immunofluorescence examinations. In vitro, quantitative real-time PCR (qRT-PCR) analysis was performed to detect the expression levels of a class of miRNAs that have positive roles in regulating wound healing. The scratch wound assay, transwell assay and cell counting kit-8 analysis were conducted to assess the effects of UCB-Exos on migration and proliferation of human skin fibroblasts and endothelial cells. Tube formation assay was carried out to test the impact of UCB-Exos on angiogenic tube formation ability of endothelial cells. Meanwhile, by using specific RNA inhibitors or siRNAs, the roles of the candidate miRNA and its target genes in UCB-Exos-induced regulation of function of fibroblasts and endothelial cells were assessed.

Results: The local transplantation of UCB-Exos into mouse skin wounds resulted in accelerated re-epithelialization, reduced scar widths, and enhanced angiogenesis. In vitro, UCB-Exos could promote the proliferation and migration of fibroblasts, and enhance the angiogenic activities of endothelial cells. Notably, miR-21-3p was found to be highly enriched in UCB-Exos and served as a critical mediator in UCB-Exos -induced regulatory effects through inhibition of phosphatase and tensin homolog (PTEN) and sprouty homolog 1 (SPRY1).

Conclusion: Our results suggest that UCB-Exos are important effectors of plasma activity and can be used as a novel promising strategy for soft tissue wound healing.

Keywords: exosomes, cord blood, wound healing, miR-21-3p.

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How to cite this article:
Hu Y, Rao SS, Wang ZX, Cao J, Tan YJ, Luo J, Li HM, Zhang WS, Chen CY, Xie H. Exosomes from human umbilical cord blood accelerate cutaneous wound healing through miR-21-3p-mediated promotion of angiogenesis and fibroblast function. Theranostics 2018; 8(1):169-184. doi:10.7150/thno.21234. Available from http://www.thno.org/v08p0169.htm