Affiliation:
1. Medical College Wuhan University of Science and Technology Wuhan Hubei China
Abstract
AbstractPurposeNucleoside‐modified messenger RNA (modRNA) holds the potential for facilitating genetic enhancement of stem cells. In this study, modRNA encoding hepatocyte growth factor (modHGF) was used to chemically modify adipose‐derived mesenchymal stem cells (ADSCs) and the effect of modified ADSCs on the activation of hypertrophic scar fibroblasts (HSFs) was evaluated.MethodsCCK‐8, wound healing, and transwell assays were utilized to evaluate the viability and migratory potential of modHGF‐engineered ADSCs and their effect on HSF activation. Reverse transcription‐polymerase chain reaction, western blot, and immunofluorescence staining were performed to detect the expression of collagen‐I (Col I), collagen‐III (Col III), alpha‐smooth muscle actin (α‐SMA), matrix metallopeptidase 1 (MMP‐1), and MMP‐3.ResultsTransfection of ADSCs with modHGF (HGF‐ADSC) resulted in enhanced production of HGF. Meanwhile, modHGF modification enhanced the viability and migration of ADSCs. Notably, culture media from HGF‐ADSCs exhibited a more potent inhibitory effect on the proliferation and migration of HSFs. In addition, culture media from HGF‐ADSCs inhibited extracellular matrix synthesis of HSFs, as evidenced by reduced expression levels of Col I, Col III, and α‐SMA, while increasing expression of MMP‐1 and MMP‐3. Conversely, neutralization experiments confirmed that these effects could be effectively alleviated by blocking HGF activity.ConclusionmodHGF modification optimizes the inhibitory effect of ADSCs on HSF activation, which provides a promising alternative for preventing and treating hyperplastic scars.