Hypoxia Mesenchymal Stem Cells Accelerate Wound Closure Improvement by Controlling α-smooth Muscle actin Expression in the Full-thickness Animal Model

Abstract

BACKGROUND: The active myofibroblast producing extracellular matrix deposition regarding wound closure is characterized by alpha-smooth muscle actin (α-SMA) expression. However, the persistence of α-SMA expression due to prolonged inflammation may trigger scar formation. A new strategy to control α-SMA expression in line with wound closure improvement uses hypoxic mesenchymal stem cells (HMSCs) due to their ability to firmly control inflammation for early initiating cell proliferation, including the regulation of α-SMA expression associated with wound closure acceleration.
 AIM: This study aimed to explore the role of HMSCs in accelerating the optimum wound closure percentages through controlling the α-SMA expression.
 MATERIALS AND METHODS: Twenty-four full-thickness rats wound model were randomly divided into four groups: Sham (Sh), Control (C) by NaCl administration only, and two treatment groups by HMSCs at doses of 1.5×106 cells (T1) and HMSCs at doses of 3×106 cells (T2). HMSCs were incubated under hypoxic conditions. The α-SMA expression was analyzed under immunohistochemistry staining assay, and the wound closure percentage was analyzed by ImageJ software.
 RESULTS: This study showed a significant increase in wound closure percentage in all treatment groups that gradually initiated on days 6 and 9 (p < 0.05). In line with the increase of wound closure percentages on day 9, there was also a significant decrease in α-SMA expression in all treatment groups (p < 0.05), indicating the optimum wound healing has preceded.
 CONCLUSION: HMSCs have a robust ability to accelerated wound closure improvement to the optimum wound healing by controlling α-SMA expression depending on wound healing phases.

Potential of stem cell seeded three-dimensional scaffold for regeneration of full-thickness skin wounds

“…myofibroblasts, endothelial cells, hair follicles etc. In the process of wound healing, migration and deposition of fibroblasts are activated, resulting in the formation of mature myofibroblasts, which are characterized by the expression of α-SMA [30,33,35]. A similar pattern was observed in our study, when the skin wound tissues were stained with angiogenic factors, VEGF and α-SMA.…”

The CD4+CD25+FoxP3+ Regulatory T Cells Regulated by MSCs Suppress Plasma Cells in a Mouse Model of Allergic Rhinitis

“…The medium was renewed every 3 days, and the cells were passaged after reaching 80% confluence. UC-MSCs at passages 4-6 were employed for the following experiments ( 9 , 26 ).…”

“…Briefly, the cultured cells were incubated in the dark with primary antibodies mouse anti-human CD29, mouse anti-human CD90, and mouse anti-human Lin negative (CD45/CD31) followed by secondary conjugated antibody. MSCs were stained with a specific antibody for 30 minutes at 4 °C, examined with a BD Accuri C6 Plus flow cytometer (BD Biosciences, San Jose, CA, USA) and analyzed with BD Accuri C6 Plus software (BD Biosciences, San Jose, CA, USA) ( 26 ).…”

Increased serial levels of platelet‐derived growth factor using hypoxic mesenchymal stem cell‐conditioned medium to promote closure acceler‐ ation in a full‐thickness wound

“…The procedures in this study were approved by the Institutional Ethics Review Board of UNISSULA University, Semarang. The isolation of MSC from an umbilical cord (UC-MSC) of 19 days pregnancy of female rat was performed using a previously described method with modification (Hamra et al 2021). Briefly, the umbilical cord was mechanically dissected and cultured in Dulbecco's modified Eagle's medium (DMEM) (Sigma-Aldrich, St. Louis, MO, USA) contained 10% fetal bovine serum (Sigma-Aldrich, St. Louis, MO, USA), 100 IU/ml penicillin/streptomycin (Sigma-Aldrich, St. Louis, MO, USA) under normoxic condition.…”