Regeneration Potential of Mesenchymal Stem Cells in Cold Induced Burn Wounds

Abstract

Background: Time-dependent initiation of wound healing phases and their associated healing mediators are crucial for injured skin regeneration. Mesenchymal stem cells (MSCs) secrete various paracrine factors which aid in wound healing via acceleration of cell migration, angiogenesis, tissue granulation, and modulation of inflammation at the wound site. Objective: This study was aimed to investigate thetherapeutic effect of human umbilical cord MSCs (hUCMSCs) in the regeneration of cold-induced burn wound model. Methods: hUCMSCs were characterized by immunocytochemistry and flow cytometry. Scratch assay was performed using rat skin fibroblasts treated with conditioned medium of hUCMSCs. An in vivo cold burn wound model was developed and hUCMSCs were locally transplanted. Macroscopic analysis of wound closure was done at days 1, 3, 7 and 14 corresponding to wound healing phases. Gene expression, histology and immunohistochemical analysis were performed to confirm complete wound repair. Results: We observed a significant reduction in the scratch area in the treated group as compared to the control. Wound area was remarkably reduced in the burn wound model transplanted with hUCMSCs well before the end of the experimental period (day 14). Histology showed intact collagen with regenerated epidermis, dermis and hair follicles, while immunohistochemistry showed enhanced angiogenesis in the last phase of healing in the treated group. Temporal gene expression showed significant reduction in inflammatory cytokines and upregulation of pro/angiogenic and remodeling cytokines at particular time points. Conclusion: It is concluded from this study that hUCMSCs accelerate wound closure with enhanced neovascularization and reduced inflammation in rat dermal wounds.