Mesenchymal Stem Cells Suppress Fibroblast Proliferation and Reduce Skin Fibrosis Through a TGF-β3-Dependent Activation

Abstract

Recent studies showed that transplantation of mesenchymal stem cells (MSCs) significantly decreased tissue fibrosis; however, little attention has been paid to its efficacy on attenuating skin fibrosis, and the mechanism involved in its effect is poorly understood. In this work, we investigated the effects of MSCs on keloid fibroblasts and extracellular matrix deposition through paracrine actions and whether the antifibrotic properties of MSCs involved transforming growth factor-β (TGF-β)-dependent activation. In vitro experiments showed that conditioned media (CM) from MSCs decreased viability, a-smooth muscle actin expression, and collagen secretion of human keloid fibroblasts. In addition, TGF-β3 secreted by MSCs was expressed at high level under inflammatory environment, and blocking the activity of TGF-β3 apparently antagonized the suppressive activity of MSC CM, which demonstrated that TGF-β3 played a preponderant role in preventing collagen accumulation. In vivo studies showed that MSC CM infusion in a mouse dermal fibrosis model induced a significant decrease in skin fibrosis. Histological examination of tissue sections and immunohistochemical analysis for α-smooth muscle actin revealed that TGF-β3 of CM-mediated therapeutic effects could obviously attenuate matrix production and myofibroblast proliferation and differentiation. These findings suggest that TGF-β3 mediates the attenuating effect of MSCs on both the proliferation and extracellular matrix production of human keloid fibroblasts and decreases skin fibrosis of mouse model, thus providing new understanding and MSC-based therapeutic strategy for cutaneous scar treatment.

Efficacy of administered mesenchymal stem cells in the initiation and co‐ordination of repair processes by resident disc cells in an ovine (Ovis aries) large destabilizing lesion model of experimental disc degeneration

“…qRT‐PCR of COL1A1, COL2A1 , ACAN , MMPs , ADAMTS4, 5 and TIMP1, 3 explained the enhanced ECM production and decreased IVDD and positive repair response. A prominent feature of MSC treatment was the lack of a fibrotic response consistent with the reduced fibrosis and hypertrophic scar formation reported in a number of studies including the IVD . This is considered to occur through the regulation of immunomodulatory processes by the MSCs suppressing inflammation and TGF‐β mediated cellular responses which otherwise can lead to excessive laying down of collagen as part of a repair response.…”

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

“…The expression of a-SMA was apparently less than that in the PBS and HEK-293T groups. Classically, the presence of a-SMA has been considered to be a marker for myofibroblast differentiation [33], because quiescent myofibroblasts do not strongly express a-SMA [34]. However, the excess differentiation of fibroblasts is an important aspect to its sustained expression.…”

BMP7‑overexpressing bone marrow‑derived mesenchymal stem cells (BMSCs) are more effective than wild‑type BMSCs in healing fractures

“…Using different inducers and methods such as dexamethasone, vitamin C, vitamin D, BMPs, TGF-β, FGF, or insulin, can induce MSCs to differentiate into different lineages such as osteoblasts, chondrocytes, fibroblasts, myoblasts and so on (9,(17)(18)(19)(20)(21)(22). The direction has been set but differentiated cells can reverse the differentiation induced under certain conditions.…”