The Role of MSC in Wound Healing, Scarring and Regeneration

Abstract

Tissue repair and regeneration after damage is not completely understood, and current therapies to support this process are limited. The wound healing process is associated with cell migration and proliferation, extracellular matrix remodeling, angiogenesis and re-epithelialization. In normal conditions, a wound will lead to healing, resulting in reparation of the tissue. Several risk factors, chronic inflammation, and some diseases lead to a deficient wound closure, producing a scar that can finish with a pathological fibrosis. Mesenchymal stem/stromal cells (MSCs) are widely used for their regenerative capacity and their possible therapeutically potential. Derived products of MSCs, such as exosomes or extravesicles, have shown a therapeutic potential similar to MSCs, and these cell-free products may be interesting in clinics. MSCs or their derivative products have shown paracrine beneficial effects, regulating inflammation, modifying the fibroblast activation and production of collagen and promoting neovascularization and re-epithelialization. This review describes the effects of MSCs and their derived products in each step of the wound repair process. As well, it reviews the pre-clinical and clinical use of MSCs to benefit in skin wound healing in diabetic associated wounds and in pathophysiological fibrosis.

Keywords: MSC; angiogenesis; extracellular matrix; fibrosis; inflammation; mesenchymal stem/stromal cells; regeneration; scar; wound healing.

Figure 1

Time lapse of cells recruited into a wound. During the first phase, platelets and neutrophils are recruited, and then monocytes are recruited and infiltrate the tissue and differentiate into macrophages; resident macrophages can also proliferate. Altogether, this leads lead to fibrocyte recruitment and fibroblast proliferation and the posterior conversion to myofibroblasts. Other cells such as lymphocytes—mainly T cells—are also recruited in low numbers at the late stages. This figure does not show the NK, dendritic cells and mast cells; usually their numbers are extremely low, but still they can play an important role on the process.

Figure 2

Wound healing process and role of mesenchymal stem/stromal cells in each step of the process. The illustration shows the cellular players in each phase and summarize the main functions of MSCs in each step. (MSC: mesenchymal stem cell; ECM: extracellular matrix; MPO: myeloperoxidase; MDA: malondialdehyde).