Stem cell therapy for chronic skin wounds in the era of personalized medicine: From bench to bedside

Abstract

With the significant financial burden of chronic cutaneous wounds on the healthcare system, not to the personal burden mention on those individuals afflicted, it has become increasingly essential to improve our clinical treatments. This requires the translation of the most recent benchtop approaches to clinical wound repair as our current treatment modalities have proven insufficient. The most promising potential treatment options rely on stem cell-based therapies. Stem cell proliferation and signaling play crucial roles in every phase of the wound healing process and chronic wounds are often associated with impaired stem cell function. Clinical approaches involving stem cells could thus be utilized in some cases to improve a body's inhibited healing capacity. We aim to present the laboratory research behind the mechanisms and effects of this technology as well as current clinical trials which showcase their therapeutic potential. Given the current problems and complications presented by chronic wounds, we hope to show that developing the clinical applications of stem cell therapies is the rational next step in improving wound care.

A Concise Review on Tissue Engineered Artificial Skin Grafts for Chronic Wound Treatment: Can We Reconstruct Functional Skin Tissue In Vitro?

“…The endogenous population of adult stem cells play a pivotal role in cutaneous wound healing. It has been demonstrated that bone marrow-derived stem cells (BMDSCs) have the ability to migrate to the injured tissues, where they proliferate and differentiate into the required cell type, including fibroblasts [35]. It was estimated that up to 20% of fibroblasts at the wound site may originally derive from BMDSCs [36].…”

“…It was estimated that up to 20% of fibroblasts at the wound site may originally derive from BMDSCs [36]. Similarly, adipose tissue-derived stem cells (ADSCs) can differentiate and regenerate damaged skin tissue, whereas re-epithelialization of the wound occurs as a consequence of differentiation of interfollicular and hair follicle bulge epithelial stem cells toward keratinocytes [35]. Revascularization of the injured skin is the effect of either proliferation of endothelial cells in existing blood vessels (angiogenesis) or differentiation of endothelial progenitor cells (vasculogenesis).…”

“…Revascularization of the injured skin is the effect of either proliferation of endothelial cells in existing blood vessels (angiogenesis) or differentiation of endothelial progenitor cells (vasculogenesis). Nevertheless, new blood vessels are formed at the wound site, mainly through the angiogenesis mechanism [37], whereas the major role of endothelial progenitor cells is to secrete pro-healing GFs [35,38].…”

Stem Cell-Friendly Scaffold Biomaterials: Applications for Bone Tissue Engineering and Regenerative Medicine

“…Bone tissue engineering (BTE) emerged as a promising solution to overcome the limitations of auto- and allografts. BTE combines concepts from bone biology and engineering techniques to design scaffolds enriched with stem cells to repair large bony defects (Bishop et al, 2017 ; Coalson et al, 2019 ; Qasim et al, 2019 ; Karakuzu-Ikizler et al, 2020 ; Wang et al, 2020a ). However, bone tissue engineering practices have yet to be realized in clinical practice due to numerous limitations or lack of efficacy.…”

Clinical Translational Potential in Skin Wound Regeneration for Adipose-Derived, Blood-Derived, and Cellulose Materials: Cells, Exosomes, and Hydrogels

“…There have been considerable advancements in the understanding of the biochemical pathways and mechanisms underlying skin regenerative therapies, leading to explorations into the use of cells and cell-derived cytokines and exosomes, as well as hydrogels (recently reviewed in [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]) ( Table 1 ). While decellularized dermal scaffolds are routinely employed [ 20 ], only a PDGF (Platelet Derived Growth Factor)-related product has received regulatory approval among the cytokines, while no cell therapy has widespread approval in the U.S. [ 21 , 22 ].…”