The Effect of Mesenchymal Stem Cells and Chitosan Gel on Full Thickness Skin Wound Healing in Albino Rats: Histological, Immunohistochemical and Fluorescent Study

BACKGROUND Wound healing involves the integration of complex biological processes. Several studies examined numerous approaches to enhance wound healing and to minimize its related morbidity. Both chitosan and mesenchymal stem cells (MSCs) were used in treating skin wounds. The aim of the current work was to compare MSCs versus chitosan in wound healing, evaluate the most efficient route of administration of MSCs, either intradermal or systemic injection, and elicit the mechanisms inducing epidermal and dermal cell regeneration using histological, immunohistochemical and fluorescent techniques. MATERIAL AND METHODS Forty adult male Sprague Dawley albino rats were divided into four equal groups (ten rats in each group): control group (Group I); full thickness surgical skin wound model, Group II: Wound and chitosan gel. Group III: Wound treated with systemic injection of MSCs and Group IV: Wound treated with intradermal injection of MSCs. The healing ulcer was examined on day 3, 5, 10 and 15 for gross morphological evaluation and on day 10 and 15 for histological, immunohistochemical and fluorescent studies. RESULTS Chitosan was proved to promote wound healing more than the control group but none of their wound reached complete closure. Better and faster healing of wounds in MSCs treated groups were manifested more than the control or chitosan treated groups. It was found that the intradermal route of administration of stem cells enhanced the rate of healing of skin wounds better than the systemic administration to the extent that, by the end of the fifteenth day of the experiment, the wounds were completely healed in all rats of this group. Histologically, the wound areas of group IV were hardly demarcated from the adjacent normal skin and showed complete regeneration of the epidermis, dermis, hypodermis and underlying muscle fibers. Collagen fibers were arranged in many directions, with significant increase in their area percent, surrounding fully regenerated hair follicles and sebaceous glands in the dermis of the healed areas more than in other groups. CONCLUSION MSCs enhanced the healing process of wound closure more than chitosan gel treatment. Furthermore, MSCs injected intradermally, were more efficient in accelerating wound healing than any other mode of treatment.