Adipose-Derived Stem Cells (ADSCs) Supplemented with Hepatocyte Growth Factor (HGF) Attenuate Hepatic Stellate Cell Activation and Liver Fibrosis by Inhibiting the TGF-β/Smad Signaling Pathway in Chemical-Induced Liver Fibrosis Associated with Diabetes

Abstract

Liver fibrosis can develop on the background of hyperglycemia in diabetes mellitus. However, xenobiotic-related factors may accelerate diabetes-associated liver fibrosis. In this study, we aimed to assess the antfibrotic effect of ADSC and HGF therapy and to establish the cellular and molecular mechanisms through in vitro and in vivo experiments. In vitro, TGF-β1-activated hepatic stellate cells (HSCs) were cocultured with ADSCs or HGF, and the expression of several fibrosis markers was investigated. The antifibrotic effect of the ADSCs, HGF, and ADSCs supplemented with HGF was further assessed in vivo on diabetic mice with liver fibrosis experimentally induced. In vitro results showed the inhibition of HSC proliferation and decrease in fibrogenesis markers. Coadministration of ADSCs and HGF on diabetic mice with liver fibrosis enhanced antifibrotic effects confirmed by the downregulation of Col I, α-SMA, TGF-β1, and Smad2, while Smad7 was upregulated. Moreover, stem cell therapy supplemented with HGF considerably attenuated inflammation and microvesicular steatosis, decreased collagen deposits, and alleviated liver fibrosis. In conclusion, the HGF-based ADSC therapy might be of interest for the treatment of liver fibrosis in diabetic patients, consecutive aggression exerts by different environmental factors.

Adipose stem cells-derived small extracellular vesicles transport Thrombospondin 1 cargo to promote insulin resistance in gestational diabetes mellitus

“…However, studies have shown that under continuous high glucose environments, the glucose metabolism, cell replication, apoptosis, and differentiation ability of ADSCs are impaired, with a more pronounced negative impact on ADSCs derived from patients with diabetes[38] Liver tissue can be damaged in the hyperglycemic environment of diabetes, leading to liver brosis. Addition of hepatocyte growth factors to ADSCs has been proposed as a method to treat liver brosis in diabetic patients [39]. Our study showed differences in the biological functions of AML-12 cells between sEV A and sEV AG .…”

Adipose stem cells-derived small extracellular vesicles transport Thrombospondin 1 cargo to promote insulin resistance in gestational diabetes mellitus

“…Liver tissue can be damaged in the hyperglycemic environment of diabetes, leading to liver fibrosis. Addition of hepatocyte growth factors to ADSCs has been proposed as a method to treat liver fibrosis in diabetic patients [ 47 ]. Our study showed differences in the biological functions of AML-12 cells between sEV A and sEV AG .…”

Ginsenoside Rb1 Interfered with Macrophage Activation by Activating PPARγ to Inhibit Insulin Resistance in Obesity

“…Studies have shown that vascular endothelial growth factor (VEGF) is an active regulator of brain-derived neurotrophic factor (BDNF) production in diabetic patients after extraction of primary retinal Müller cells [ 21 ]. Sami [ 22 ] demonstrated that hepatocyte growth factor (HGF)-based ADSC therapy may be useful in the treatment of liver fibrosis in diabetic patients. Thus, the primary cell co-culture model was used as a whole model to simulate the body tissue or organ, and the stress response of macrophages was studied under the condition of adipose tissue obesity.…”