Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model

Shang-Chun Guo^1*, Shi-Cong Tao^2*, Wen-Jing Yin², Xin Qi², Ting Yuan^2✉, Chang-Qing Zhang^{1, 2✉}

1. Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China;
2. Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
* Co-first authors: These authors contributed equally to this work.

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Citation:
Guo SC, Tao SC, Yin WJ, Qi X, Yuan T, Zhang CQ. Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model. Theranostics 2017; 7(1):81-96. doi:10.7150/thno.16803. Available from http://www.thno.org/v07p0081.htm

Abstract

Chronic wounds have become an economic, social, and public health burden and need advanced treatment. Platelet-rich plasma (PRP) has been used extensively in treatment of chronic wounds because it contains an abundance of growth factors secreted by platelets. The exosomes derived from PRP (PRP-Exos) have been proven to encapsulate principal growth factors from platelets. This study is the first to show that these exosomes may exert the function of PRP. PRP-Exos can effectively induce proliferation and migration of endothelial cells and fibroblasts to improve angiogenesis and re-epithelialization in chronic wounds. We regulated YAP to verify the PRP-Exos-dependent effect on fibroblast proliferation and migration through YAP activation. In vivo, we observed the cutaneous healing process in chronic wounds treated with PRP-Exos in a diabetic rat model. We provide evidence of the probable molecular mechanisms underlying the PRP effect on healing of chronic ulcers and describe a promising resource of growth factors from exosomes without species restriction.

Keywords: chronic wounds, platelet-rich plasma (PRP), exosomes, Yes-associated protein, re-epithelization.