Panoply™ Human HGF Over-expressing Stable Cell Line

Numerous studies have explored the advantages of using mesenchymal stem cells (MSCs)-which secrete a variety of paracrine factors-to repair endometrial injury. However, further improvements in stability and therapeutic efficacy are required for MSCs to become a viable treatment modality. Hepatocyte growth factor (HGF) is one of the cytokines secreted by MSCs; it promotes vascular repair and mesenchymal-to-epithelial transition (MET). Consequently, HGF is likely to facilitate the process of endometrial repair. In this study, researchers generated HGF-transfected MSCs and utilized a mouse model of endometrial injury to investigate their reparative effects and underlying mechanisms. The results demonstrated that the transfected MSCs retained their original cellular characteristics while exhibiting significantly elevated HGF expression levels. In the mouse model, HGF-overexpressing MSCs facilitated the restoration of endometrial morphology, promoted endometrial cell proliferation while inhibiting apoptosis, upregulated the expression of factors associated with endometrial angiogenesis, and activated the phosphorylated c-Met and AKT signaling pathways. Compared with unmodified MSCs, HGF-overexpressing MSCs exerted a more pronounced promoting effect on the repair of damaged endometrial epithelium through the activation of the HGF/c-Met axis and its downstream signaling pathways. These findings indicate that HGF-transfected MSCs represent an effective and promising therapeutic strategy for treating endometrial injury.

To verify the reparative capacity of HGF, the researchers analyzed the proliferation and apoptosis of epithelial cells. MSCs transfected with the HGF gene enhanced the proliferative capacity of damaged endometrial epithelial cells (Figure 1a). Statistical analysis of Ki-67 fluorescence intensity revealed that the proliferative effect of HGF-overexpressing MSCs was significantly greater than that observed in the normal saline and MSC groups (Figure 1b). Furthermore, the researchers quantitatively assessed the anti-apoptotic effect of HGF-overexpressing MSCs by analyzing TUNEL fluorescence intensity (Figure 1c). Notably, the level of apoptotic cells in the HGF-overexpressing MSC group was lower than that in the normal saline and MSC groups (Figure 1d).

Figure 1. HGF-overexpressing MSCs increase proliferation and decrease apoptosis of endometrial cells in the uterus. (Xu X, et al., 2022)