International Journal of Nanomedicine (Dec 2022)

Enhancing Cutaneous Wound Healing Based on Human Induced Neural Stem Cell-derived Exosomes

  • Li J,
  • Gao H,
  • Xiong Y,
  • Wang L,
  • Zhang H,
  • He F,
  • Zhao J,
  • Liu S,
  • Gao L,
  • Guo Y,
  • Deng W

Journal volume & issue
Vol. Volume 17
pp. 5991 – 6006

Abstract

Read online

Jing Li,* Hong Gao,* Yue Xiong,* Ling Wang, Haojie Zhang, Fumei He, Jingxin Zhao, Shuna Liu, Liqian Gao, Ying Guo, Wenbin Deng School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying Guo; Wenbin Deng, Email [email protected]; [email protected]: Wound healing of skin is a complicated process. Cutaneous innervation and neurotrophic factors could participate in multiple stages of wound healing. Neurotrophic factors are mainly produced and released by neurons and neural stem cells (NSCs) which could be obtained in large quantities from human-induced pluripotent stem cells (iPSCs) in vitro. However, the potential wound healing effects of NSC secretions, such as exosomes, are unexplored yet.Methods: NSCs-derived exosomes (NSC-exo) and iPSCs-derived exosomes (iPSC-exo) were isolated from the cell culture supernatants by centrifugation, and then quantified and characterized. The effects of these exosomes on the migration of human dermal fibroblasts (HDF) cells and the tube formation of human umbilical vein endothelial cells (HUVECs) were investigated in vitro. And the in vivo wound healing effect of these exosomes were tested on the mouse skin trauma model. Therefore, a dipeptide/hyaluronic acid (Nap-FF/HA) composite hydrogel was used to encapsulate the exosomes as a sustained release carrier. Histological observations were performed to evaluate the wound healing effect of exosomes. Furthermore, the non-labeling proteomic analysis was performed to explore the possible mechanisms of NSC-exo on wound healing.Results: We obtained extracellular vesicles in a bowl-like structure with membranes which meet the general standards of exosomes. NSC-exo showed promotion effect on the migration of HDF cells and the tube formation of HUVECs in vitro. In a mouse skin injury model, NSC-exo enhanced the wound healing and the Nap-FF/HA hydrogel that contained exosomes did so with less drug frequency by sustaining release of exosomes. Further proteomic analysis demonstrated that the carried neurotrophic factors and immunity-related proteins in NSC-exo may play a functional role in wound healing.Conclusion: NSC-exo may enhance wound healing via neurotrophic factors and immunomodulation.Graphical Abstract: Keywords: wound healing, neural stem cells, exosomes, proteomic analysis

Keywords