Evaluation of epithelial progenitor cells and growth factors in a preclinical model of wound healing induced by mesenchymal stromal cells.

Carlos Ayala-Grosso,Olga Wittig,Lianeth Salazar,Giselle Ramos-Gonzalez,Dylana Diaz-Solano,Jose E Cardier

doi:10.1042/bsr20200461

Carlos Ayala-Grosso, Olga Wittig + Show 4 more

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https://doi.org/10.1042/bsr20200461

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Abstract

Background: Skin wounds continue to be a global health problem. Several cellular therapy protocols have been used to improve and accelerate skin wound healing. Here, we evaluated the effect of transplantation of mesenchymal stromal cells (MSC) on the wound re-epithelialization process and its possible relationship with the presence of epithelial progenitor cells (EPC) and the expression of growth factors. Methods: An experimental wound model was developed in C57BL/6 mice. Human MSCs seeded on collagen membranes (CM) were implanted on wounds. As controls, animals with wounds without treatment or treated with CM were established. Histological and immunohistochemical (IH) studies were performed at day 3 post-treatment to detect early skin wound changes associated with the presence of EPC expressing Lgr6 and CD34 markers and the expression of keratinocyte growth factor (KGF) and basic fibroblast growth factor (bFGF). Results: MSC transplantation enhanced skin wound re-epithelialization, as compared with controls. It was associated with an increase in Lgr6+ and CD34+ cells and the expression of KGF and bFGF in the wound bed. Conclusion: Our results show that cutaneous wound healing induced by MSC is associated with an increase in EPC and growth factors. These preclinical results support the possible clinical use of MSC to treat cutaneous wounds.

Highlights

Cutaneous wound healing comprises several stages; one of them is the re-epithelialization, which is fundamental for tissue wound repair [1] It initiates with the activation, migration and proliferation of epithelial progenitor cells (EPC) located in the interfollicular epidermis (IFE) and hair follicles (HFs) [2]
mesenchymal stromal cells (MSC)/collagen membranes (CM) were removed from the inserts and cut to the size of the wound (Figure 3C), and turned MSC side downward on to the wound bed (Figure 3D)
Based on evidence showing that EPC (Lgr6+ and CD34+ cells) are involved in skin wound repair [24], we evaluated whether re-epithelialization of wounds induced by MSC transplantation was associated with the presence of these cells

Summary

Introduction

Cutaneous wound healing comprises several stages; one of them is the re-epithelialization, which is fundamental for tissue wound repair [1] It initiates with the activation, migration and proliferation of epithelial progenitor cells (EPC) located in the interfollicular epidermis (IFE) and hair follicles (HFs) [2]. Numerous studies have focused on the use of mesenchymal stromal cells (MSC) transplantation for inducing wound repair [5,6,7,8]. We evaluated the effect of transplantation of mesenchymal stromal cells (MSC) on the wound re-epithelialization process and its possible relationship with the presence of epithelial progenitor cells (EPC) and the expression of growth factors. Results: MSC transplantation enhanced skin wound re-epithelialization, as compared with controls It was associated with an increase in Lgr6+ and CD34+ cells and the expression of KGF and bFGF in the wound bed. Conclusion: Our results show that cutaneous wound healing induced by MSC is associated with an increase in EPC and growth factors. These preclinical results support the possible clinical use of MSC to treat cutaneous wounds

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