Effect of Human Umbilical Cord Mesenchymal Stem Cells Transfected with HGF on TGF-β1/Smad Signaling Pathway in Carbon Tetrachloride-Induced Liver Fibrosis Rats

Abstract

The research on human umbilical cord-derived mesenchymal stem cells (hUCMSCs) suggests promising therapeutic strategy for ameliorating liver fibrosis and it can be an effective alternative method of orthotopic liver transplantation. Hepatocyte growth factor (HGF) is the most basic cytokine involved in the inhibition of liver fibrosis and promotion of hepatocyte proliferation and regeneration. The objective of this study was to determine the possible mechanism about how the microencapsulated hUCMSCs made by alginate-poly-lysine-alginate (A-P-A) transfected with HGF could ameliorate liver fibrosis through the TGF-β1/Smad signaling pathway. The microencapsulated cells were divided into four groups: hUCMSC (microcapsules of hUCMSCs), HGF (microcapsules of HGF+hUCMSCs), LV5-NC (microcapsules of LV5-NC, an rLV-EF1a-EGFP+Puro control lentiviral vector+hUCMSCs), and empty microcapsule (microcapsules without any hUCMSCs), and then transplanted by intraperitoneal injection into carbon tetrachloride (CCl₄)-induced liver fibrosis rats, respectively. The results showed that the fibrosis in the hUCMSC, LV5-NC, and HGF groups was significantly alleviated. Moreover, the messenger RNA (mRNA) and protein levels of collagen I, collagen III, α-SMA, TGF-β1, Smad2, and Smad3 were significantly decreased compared with the empty microcapsule group and these indices in HGF group were more decreased compared with hUCMSC and LV5-NC groups. This study indicated that microencapsulated hUCMSCs transfected with HGF could effectively improve CCl₄-induced rat liver fibrosis and the possible mechanism was closely related to the inhibition of TGF-β1/Smad signaling pathway.

Keywords: A-P-A microcapsule; TGF-β1/Smad signaling pathway; cell therapy; hepatocyte growth factor; human umbilical cord mesenchymal stem cells; liver fibrosis.