Background: The skin can be damaged by wounds caused by cutting or breaking of the tissue and burns. As a result of their secreted factors with anti-inflammatory, anti-fibrotic, and pro-angiogenic activities, mesenchymal stem cells (MSCs) are able to improve wound healing in a number of ways. These factors can either be expressed encapsulated inside membrane vesicles (microparticles and exosomes) or in soluble molecules (growth factors, cytokines). To summarize how mesenchymal stem cells influence wound healing and describe the latest approaches to enhance their therapeutic value in non-healing wounds, this review aims to summarize the mechanisms underlying that effect. Methods: Nine databases (PubMed, Scopus, Google Scholar, Cochrane Library, Magiran, SID, Medline, Embase, and Lilacs) were searched for published articles on Mesenchymal Stem Cell-Based therapy for chronic wound healing from January 2000 to January 2023. Fifteen affiliated articles with complete abstracts were included in this study. All data were extracted from interconnected papers and analyzed with R version 4.2.1 artificial intelligence software. Results: MSCs can act indirectly through the secretion of immunomodulatory and bioactive factors. Several growth factors produce growth factors that stimulate cell proliferation and survival, including VEGF, HGF, and leukemia inhibitory factors (LIF). MSCs also produce interleukin (IL)-6 and 10 as well as prostaglandin E-2 (PGE-2), transforming growth factor (TGF), or nitric oxide (NO). As a result, they inhibit T lymphocyte proliferation, inhibit T lysis, prevent NK cell activation and macrophage activation, and modulate B cell proliferation, among other immunomodulating effects. Conclusion: In conclusion, mesenchymal stem cells (MSCs) are able to improve wound healing, and they secrete factors that have anti-inflammatory, antifibrotic, and pro-angiogenic functions, which have been shown to play a significant role in wound healing.

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