The Role and Prospects of Mesenchymal Stem Cells in Skin Repair and Regeneration

Abstract

Mesenchymal stem cells (MSCs) have been recognized as a cell therapy with the potential to promote skin healing. MSCs, with their multipotent differentiation ability, can generate various cells related to wound healing, such as dermal fibroblasts (DFs), endothelial cells, and keratinocytes. In addition, MSCs promote neovascularization, cellular regeneration, and tissue healing through mechanisms including paracrine and autocrine signaling. Due to these characteristics, MSCs have been extensively studied in the context of burn healing and chronic wound repair. Furthermore, during the investigation of MSCs, their unique roles in skin aging and scarless healing have also been discovered. In this review, we summarize the mechanisms by which MSCs promote wound healing and discuss the recent findings from preclinical and clinical studies. We also explore strategies to enhance the therapeutic effects of MSCs. Moreover, we discuss the emerging trend of combining MSCs with tissue engineering techniques, leveraging the advantages of MSCs and tissue engineering materials, such as biodegradable scaffolds and hydrogels, to enhance the skin repair capacity of MSCs. Additionally, we highlight the potential of using paracrine and autocrine characteristics of MSCs to explore cell-free therapies as a future direction in stem cell-based treatments, further demonstrating the clinical and regenerative aesthetic applications of MSCs in skin repair and regeneration.

Keywords: mesenchymal stem cells; skin regeneration; skin rejuvenation; wound healing.

Figure 1

Schematic depiction of wound healing phases and the corresponding cellular responses. In the initial phase of wound healing, when blood clotting occurs, platelets release signaling molecules and chemical messengers that attract inflammatory cells. Inflammation begins with the influx of neutrophils, facilitated by the release of histamine from mast cells. Subsequently, monocytes arrive and differentiate into tissue macrophages, which are responsible for clearing residual cell debris and neutrophils. In the proliferative phase, keratinocytes migrate to bridge the wound, new blood vessels form through the growth of tiny vessels, and specialized cells called fibroblasts replace the initial blood clot with a tissue known as granulation tissue. Macrophages and regulatory T cells play crucial roles during this stage of the healing process. Eventually, the newly formed tissue undergoes further restructuring as fibroblasts reshape the deposited matrix, the blood vessels diminish in size, and specialized cells called myofibroblasts contribute to the overall contraction of the wound. Reproduced with permission from [23].

Figure 2

Schematic diagram illustrating the two primary sources of mesenchymal stem cells: adult-derived and perinatal-derived sources. Reproduced with permission from [27].

Figure 3

Illustration depicting the impact of MSC-derived EVs on the process of wound healing. Reproduced with permission from [55].