Hepatocyte Growth Factor Gene-Modified Mesenchymal Stem Cells Augment Sinonasal Wound Healing

Abstract

This study was designed to investigate the effects of hepatocyte growth factor (HGF) transgenic mesenchymal stem cells (HGF-MSCs) on wound healing in the sinonasal mucosa and nasal epithelial cells (NECs). We also sought to determine whether HGF-MSCs and MSCs can migrate into the injured mucosa and differentiate into ciliated cells. Human HGF-overexpressing umbilical cord MSCs (hHGF-UCMSCs) were established, and upregulation of hHGF expression was confirmed by real-time PCR (RT-PCR) and enzyme-linked immunosorbant assay (ELISA). To investigate the paracrine effect of human MSCs (hMSCs) on nasal epithelial repair, hMSC-and HGF-MSC-conditioned media (CM) were used in NEC proliferation assays and in an in vitro scratch-wound repair model. The in vivo sinonasal wound-healing model was established, and all enrolled rabbits were randomly assigned to four groups: the GFP-MSC group, the HGF-MSC group, the Ad-HGF group, and the surgery control group. The average decreased diameter was recorded, and the medial wall of the maxillary sinus was removed for histological analysis and scanning electron microscopy. Collagen deposition in the wound tissue was detected via Masson trichrome (M&T) staining. The distribution of MSCs and HGFMSCs was observed by immunofluorescence. MSCs improved nasal wound healing both in vivo and in vitro. HGF overexpression in MSCs augmented the curative effects. Reduced collagen deposition and transforming growth factor beta1 (TGF-b1) expression were detected in the HGF-MSC group compared with the MSC-, Ad-HGF-, and phosphate-buffered saline-treated groups based on M&T staining and ELISA. The enhanced therapeutic effects of HGF-MSCs were accompanied by decreased level of the fibrogenic cytokine TGF-b1. In addition, both HGF-MSCs and MSCs can migrate to the injured mucosa and epithelial layer.

Effects of JWH015 in cytokine secretion in primary human keratinocytes and fibroblasts and its suitability for topical/transdermal delivery

“…This in vitro assay is widely used to study some functional aspects of keratinocytes and fibroblasts in the wound healing process. 36 – 38 We conducted this experiment to determine whether the immunomodulatory effects of JWH015 on keratinocytes and fibroblasts affect their migration capabilities.…”

“…The migration capabilities of these cells to fill the scratch gap mimic a wound healing process. 36 , 37 This process was measured at base line (0 h), and at 4, 12, 17 and 24 h following the scratch. Six digital images (5×) per condition were taken at each time point in the same area, next to a line of reference that was drawn previously.…”

Umbilical Cord as Prospective Source for Mesenchymal Stem Cell-Based Therapy

“…There is little evidence for the differentiation of UC-MSCs into relevant cells; it may be related to xenogeneic transplantation used in most of the studies. Presently, proposed mechanisms of UC-MSCs therapeutic activity include trophic and paracrine effects on cells of the immune system, remodeling of the extracellular matrix, angiogenesis, apoptosis, and stimulation of the migration and proliferation of resident progenitor cells [ 18 , 19 , 21 – 29 , 31 , 104 ]. All of the studies show amazing prospects for clinical use of UC-MSCs.…”

IL-10 Gene-Modified Human Amniotic Mesenchymal Stem Cells Augment Regenerative Wound Healing by Multiple Synergistic Effects

“…Alapure et al found that bone marrow MSCs with incorporated biomaterial covering burn wounds promote closure, reepithelialization, granulation tissue formation, and vascularization of burn wounds [5]. Modification of MSCs by hepatocyte growth factor and vascular endothelial growth factor (VEGF) genes to increase necessary biological effects and augment wound healing has been confirmed [6, 7].…”