What is the role of Mesenchymal Stem Cells in Wound Regeneration?

Mesenchymal stem cells (MSCs) are essential to the wound-healing process, especially for problematic non-healing wounds caused by trauma, diabetes, vascular insufficiency, and a variety of other disorders. Due to their role in the inflammatory, proliferative, and remodelling phases of wound healing, MSCs encourage normal physiologic function in the direction of efficient repair. Therefore, when employed therapeutically, MSCs have been shown to promote and improve wound recovery in medical applications.

Wound healing is a dynamic and intricate process that involves numerous coordinated actions, such as bleeding and coagulation, acute inflammation, cell migration, proliferation, differentiation, angiogenesis, re-epithelialization, and the synthesis and remodelling of ECM. These intricate processes take place in the phases of (a) inflammation, (b) proliferation, and (c) remodelling.

An overview of the mechanism of wound repair by MSCs

However, MSCs are involved in these processes by first directly reducing the inflammatory response, as the presence of MSCs reduces the release of the proinflammatory cytokines TNF-α and IFN-γ, while simultaneously enhancing the synthesis of the anti-inflammatory cytokines’ IL-10 and IL-4. Secondly, MSCs release a variety of cytokines, chemokines, and growth factors known as tissue repair mediators, including VEGF, PDGF, bFGF, EGF, KGF, and TGF-β, which affect an array of cell types, including epithelial, endothelial, keratinocyte, and fibroblasts, to promote cell survival, proliferation, and migration. Finally, ECM remodelling is crucial for effective wound healing, which is mainly controlled by matrix metalloproteinase (MMP). Interestingly, Matrix metalloproteinase (MMP)-1 expression has been demonstrated to be inhibited by MSCs, suggesting that MSCs prevent the breakdown of the collagenous matrix, retain the matrix and aid in fibroblast regeneration.

MSCs’ wound healing efficacy is being improved by researchers

In addition to the standard MSC injection, researchers have also found ways to increase the ability of wounds to regenerate by using specialized substances for skin engraftment like fibrin polymer spray, which may accelerate the healing of chronic, long-lasting, non-healing lower extremity wounds in patients, or by directly incorporating matrix or hydrogel into the wound to increase the MSCs’ repairing and therapeutic effects. In addition, by releasing paracrine factors, MSCs seeded on the scaffold were able to significantly improve the quality of the skin that was being regenerated, reduce the amount of collagen that was being deposited, promote neo-angiogenesis and re-epithelialization, and ultimately sustain a more significant return of hair follicles.

In conclusion, MSCs can be extracted from a variety of sources, including bone marrow, adipose tissue, umbilical cord, placenta, and peripheral blood, in the therapeutic context. Exosomes, conditioned media, and viable MSCs have all been used in clinical applications as therapeutic components. Several research studies have also shown promising results in therapeutic applications on diseases such as neurological diseases, brain tumours, and bone and cartilage regeneration. However, numerous issues still need to be resolved, including the standardization of culture conditions and immunological adverse effects.

References

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• Guillamat-Prats R. The Role of MSC in Wound Healing, Scarring and Regeneration. Cells. 2021 Jul 8; 10(7): 1729.
• Lee DE, Ayoub N, Agrawal DK. Mesenchymal stem cells and cutaneous wound healing: novel methods to increase cell delivery and therapeutic efficacy. Stem Cell Res Ther. 2016 Mar 9; 7: 37.
• Maxson S, Lopez EA, Yoo D, Danilkovitch-Miagkova A, Leroux MA. Concise review: role of mesenchymal stem cells in wound repair. Stem Cells Transl Med. 2012 Feb; 1(2): 142-9.
• Brembilla NC, Vuagnat H, Boehncke WH, Krause KH, Preynat-Seauve O. Adipose-Derived Stromal Cells for Chronic Wounds: Scientific Evidence and Roadmap Toward Clinical Practice. Stem Cells Transl Med. 2023 Jan 30; 12(1): 17-25.