Hepatocyte growth factor-modified adipose-derived mesenchymal stem cells inhibit human hypertrophic scar fibroblast activation.

Purpose: Nucleoside-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.

Methods: CCK-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.

Results: Transfection 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.

Conclusion: modHGF modification optimizes the inhibitory effect of ADSCs on HSF activation, which provides a promising alternative for preventing and treating hyperplastic scars.