Human Wharton’s jelly mesenchymal stem cells promote skin wound healing through paracrine signaling

Abstract

IntroductionThe prevalence of nonhealing wounds is predicted to increase due to the growing aging population. Despite the use of novel skin substitutes and wound dressings, poorly vascularized wound niches impair wound repair. Mesenchymal stem cells (MSCs) have been reported to provide paracrine signals to promote wound healing, but the effect of human Wharton’s jelly-derived MSCs (WJ-MSCs) has not yet been described in human normal skin.The aim of this study is to examine the effects of human WJ-MSC paracrine signaling on normal skin fibroblasts in vitro, and in an in vivo preclinical model.MethodsHuman WJ-MSCs and normal skin fibroblasts were isolated from donated umbilical cords and normal adult human skin. Fibroblasts were treated with WJ-MSC-conditioned medium (WJ-MSC-CM) or nonconditioned medium.ResultsExpression of genes involved in re-epithelialization (transforming growth factor-β2), neovascularization (hypoxia-inducible factor-1α) and fibroproliferation (plasminogen activator inhibitor-1) was upregulated in WJ-MSC-CM-treated fibroblasts (P ≤ 0.05). WJ-MSC-CM enhanced normal skin fibroblast proliferation (P ≤ 0.001) and migration (P ≤ 0.05), and promoted wound healing in an excisional full-thickness skin murine model.ConclusionsUnder our experimental conditions, WJ-MSCs enhanced skin wound healing in an in vivo mouse model.

Umbilical Cord-Derived Mesenchymal Stem Cell-Derived Exosomal MicroRNAs Suppress Myofibroblast Differentiation by Inhibiting the Transforming Growth Factor-β/SMAD2 Pathway During Wound Healing

“…Also, uMSCs are considered to be advantageous compared with bone marrow-derived MSCs and adipose-derived MSCs owing to their better potential to differentiate into other tissues and their higher capacity in proliferation [29][30][31]. However, the difference in function among these cells and especially the difference in exosomes produced is still unclear, which could be a goal of our future studies.…”

Human umbilical cord mesenchymal stem cells: an overview of their potential in cell-based therapy

“…[81,82]. These released factors may make contributions to preventing the adjacent cells from apoptosis, promoting angiogenesis, modulating inflammation and activating the intra-stem cells, which help to create a friendly environment for intrinsic restorative processes [83]. The paracrine effects of HUC-MSCs are supported by both in vitro and in vivo studies.…”

Methodologies in creating skin substitutes

“…A specific population of UMSCs, Wharton’s jelly-derived MSCs (WJMSCs), are less immunogenic, a trait that may fully prevent skin graft rejection and improve efficacy of skin substitutes[144]. It has recently been shown that WJMSCs secretome promotes skin healing without excessive fibrosis from hyper-proliferating fibroblasts[145]. Further studies are needed regarding the benefits of their reduced immunogenicity in skin regeneration when compared to other MSC sources.…”