Current regenerative medicine-based approaches for skin regeneration: A review of literature and a report on clinical applications in Japan

Abstract

Current trends indicate a growing interest among healthcare specialists and the public in the use of regenerative medicine-based approaches for skin regeneration. The approaches are categorised in either cell-based or cell-free therapies and are reportedly safe and effective. Cell-based therapies include mesenchymal stem cells (MSCs), tissue induced pluripotent stem cells (iPSCs), fibroblast-based products, and blood-derived therapies, such as those employing platelet-rich plasma (PRP) products. Cell-free therapies primarily involve the use of MSC-derived extracellular vesicles/exosomes. MSCs are isolated from various tissues, such as fat, bone marrow, umbilical cord, menstrual blood, and foetal skin, and expanded ex vivo before transplantation. In cell-free therapies, MSC exosomes, MSC-derived cultured media, and MSC-derived extracellular vesicles are collected from MSC-conditioned media or supernatant. In this review, a literature search of the Cochrane Library, MEDLINE (PubMed), EMBASE, and Scopus was conducted using several combinations of terms, such as 'stem', 'cell', 'aging', 'wrinkles', 'nasolabial folds', 'therapy', 'mesenchymal stem cells', and 'skin', to identify relevant articles providing a comprehensive update on the different regenerative medicine-based therapies and their application to skin regeneration. In addition, the regulatory perspectives on the clinical application of some of these therapies in Japan are highlighted.

Keywords: AD-MSCs, adipose MSCs; Autologous transplantation; BM-MSCs, bone marrow MSCs; Cell-based therapy; Cell-free therapy; FD-MSC, fatal dermis MSCs; IGF, insulin-like growth factor; KGF, keratinocyte growth factor; MMP-12, matrix metalloproteinase-12; MSC-CM, MSC-derived conditioned media; MSC-EVs, MSC-derived extracellular vesicles; MSC-exo, MSC-derived exosomes; MSCs, mesenchymal stem cells; Mesenchymal stem cells; NF-κB, nuclear factor-κB; PRP, platelet-rich plasma; Skin ageing; Skin regeneration; TNF-α, tumour necrosis factor alpha; TSG-6, tumour necrosis factor-stimulated gene-6; UC-MSC, umbilical cord MSCs; UVB, ultraviolet-B; VEGF, vascular endothelial growth factor; bFGF, fibroblast growth factor-basic; eMSC, endometrial mesenchymal stem-like cells; iPSCs, induced pluripotent stem cells.