Bone marrow‐derived mesenchymal stem cell attenuates skin fibrosis development in mice

Abstract

marrow-derived mesenchymal stem cell attenuates skin fibrosis development in mice. Int Wound J 2014; 11:701-710 Abstract Recent studies showed that mesenchymal stem cell (MSC) transplantation significantly alleviated tissue fibrosis; however, little is known about the efficacy on attenuating cutaneous scar formation. In this study, we established a dermal fibrosis model induced by bleomycin and evaluated the benefit of bone marrow-derived mesenchymal stem cells (BM-MSCs) on skin fibrosis development. Tracing assay of green fluorescent protein (GFP + )BM-MSCs showed that the cells disappeared gradually within 24 hours upon administration, which hinted the action of BM-MSCs in vivo was exerted in the initial phase of repair in this model. Therefore, we repeatedly transplanted syngeneic BM-MSCs in the process of skin fibrosis formation. After 3 weeks, it was found that BM-MSC-treated lesional skin demonstrated a unanimous basket-weave organisation of collagen arrangement similar to normal skin, with few inflammatory cells. In addition, lesional skin with BM-MSC treatment exhibited a significant down-regulation of transforming growth factor-β1 (TGF-β1), type I collagen and heat-shock protein 47 (HSP47), with higher expression of matrix metalloproteinases (MMPs)-2, -9 and -13. Further experiments showed that α-smooth muscle actin (α-SMA) positive cells, the most reliable marker of myofibroblasts, apparently decreased after BM-MSC transplantation, which revealed that BM-MSCs could attenuate myofibroblast proliferation and differentiation as well as matrix production. Taken together, these findings suggested that BM-MSCs can inhibit the formation process of bleomycin-induced skin fibrosis, alleviate inflammation and favour the remodelling of extracellular matrix.

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

“…In the case of wound healing, uMSCs attenuate tissue damage, inhibit fibrotic remodeling and apoptosis, promote angiogenesis, stimulate endogenous stem cell recruitment and proliferation, and reduce immune responses. However, the prevalent hypothesis has shown that, when used in cell-based therapy, uMSCs mainly provide benefits for wound healing via paracrine mechanisms [18,32]. Despite the early accumulation of systemically administered uMSCs at the site of injury, few uMSCs become permanently engrafted within the tissue.…”

“…With the recognition that transplanted MSCs are not retained in organs for longer periods [18][19][20] (supplemental online Fig. 1A), we then suggested that their paracrine ability might play a key role in exerting their functions in promoting wound repair.…”

Mesenchymal Stem Cells in Chronic Wounds: The Spectrum from Basic to Advanced Therapy

“…7 Present reports show that MSCs can decrease fibrosis in a mouse model. 117 Systemic therapies aimed at global immune suppression can improve the healing process, but the quality of healing may be compromised through a weakened scar formation. It is possible that MSCs can sense the degree of inflammation in the microenvironment and respond by releasing of growth factors, cytokines, and other mediators to reduce inflammation using real-time biochemical cues.…”

Activity of mesenchymal stem cells in therapies for chronic skin wound healing

“…Ultimately, reduced scar formation is not an outcome desired specifically for chronic wounds, but nevertheless is a significant potential benefit of utilizing MSCs to promote closure of such non-healing wounds. Experimentally, recent experimental evidence has shown that MSCs can indeed reduce a fibrotic phenotype in a mouse model, 93 showing promise for reduced scar formation in future MSC therapeutics.…”