Adipose tissue‐derived stem cells prevent fibrosis in murine steatohepatitis by suppressing IL‐17‐mediated inflammation

Abstract

Background and Aim The pathological features of non‐alcoholic steatohepatitis (NASH) have not been determined, so fundamental treatment has not been established. Adipose‐tissue‐derived stromal/stem cells (ADSCs) are beneficial for repair/regenerative therapy of impaired organs because of their immuno‐modulatory capability. In this study, we assessed how liver damage progresses during the early development phase of the murine NASH model and investigated whether ADSCs are preventatively efficacious against the fibrosis progression of NASH. Methods C57BL/6J mice were fed with atherogenic high fat or high‐fat diet 60 developing into NASH or simple steatosis. Their hepatic inflammatory cells (HICs) were analyzed by cDNA microarray. NASH mice were treated with ADSCs injected into spleen when hepatic inflammation was initially observed, and liver samples were analyzed. The effect of ADSCs on the mice hepatic stellate cell (HSC) line stimulated by recombinant IL‐17 and HICs from NASH mice was analyzed. Results The gene expression features of HICs implicated as humoral cytokine mediators of lymphoid cells during NASH development, compared with a simple steatosis model. One of the featured cytokines was IL‐17. The development of hepatic fibrosis was alleviated when NASH mice were treated with ADSCs as well as treated with anti‐IL‐17 antibody, and the frequency of IL‐17‐secreting HICs decreased. NASH‐HICs enhanced proliferation of HSCs, in which proliferation was sensitive to IL‐17 stimulation. The stimulatory effect of NASH‐HICs on the activation of HSCs was attenuated by co‐culture with ADSCs. Conclusion ADSCs treatment prevented progression of NASH fibrosis by suppressing IL‐17‐mediated inflammation, which was associated with HSCs activation.

Antioxidant preconditioning improves therapeutic outcomes of adipose tissue-derived mesenchymal stem cells through enhancing intrahepatic engraftment efficiency in a mouse liver fibrosis model

“…Regenerative medicine using adipose tissue-derived mesenchymal stem cell (ADSC) transplantation provides a promising alternative strategy for chronic liver disease treatment by using the intrinsic abilities of ADSCs including multilineage differentiation potential, self-renewal and immunomodulation properties. In particular, ADSC transplantation has been widely used for treating liver fibrosis [2], non-alcoholic liver diseases [1,[3][4][5], and cirrhosis [6] in the pre-clinical studies; but the long-term therapeutic outcomes are very poor and far from satisfaction, due to the extremely low hepatic engraftment efficiency of ADSCs. In most cases, the hepatic retention of stem cells is less than 5% after cell infusion for 4 weeks [7].…”

Antioxidant preconditioning improves therapeutic outcomes of adipose tissue-derived mesenchymal stem cells through enhancing intrahepatic engraftment efficiency in a mouse liver fibrosis model

“…Author details 1 The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University; 2 Liver Disease Center, The First A liated Hospital of Fujian Medical University; 3 Mengchao Med-X Center, Fuzhou University; 4 The Liver Center of Fujian Province, Fujian Medical University.…”

“…Chronic liver diseases are typically characterized by the intrahepatic in ammation, oxidative stress and development of liver brosis, and eventually leading to liver cirrhosis [1]. Liver transplantation is the most effective strategy for treating end-stage liver diseases including liver cirrhosis, but it is suffered from shortage of donated livers in real clinical practice.…”

“…Regenerative medicine using adipose tissue-derived mesenchymal stem cell (ADSC) transplantation provides a promising alternative strategy for chronic liver disease treatment by using the intrinsic abilities of ADSCs including multilineage differentiation potential, self-renewal and immunomodulation properties. In particular, ADSC transplantation has been widely used for treating liver brosis [2], non-alcoholic liver diseases [1,[3][4][5], and cirrhosis [6] in the pre-clinical studies; but the long-term therapeutic outcomes are very poor and far from satisfaction, due to the extremely low hepatic engraftment e ciency of ADSCs. In most cases, the hepatic retention of stem cells is less than 5% after cell infusion for 4 weeks [7].…”

Antioxidant preconditioning improves therapeutic outcomes of adipose tissue-derived mesenchymal stem cells through enhancing intrahepatic engraftment efficiency in a mouse liver fibrosis model

“…Chronic liver diseases are typically characterized by the intrahepatic inflammation, oxidative stress and development of liver fibrosis, and eventually leading to liver cirrhosis [1]. Liver transplantation is the most effective strategy for treating end-stage liver diseases including liver cirrhosis, but it is suffered from shortage of donated livers in real clinical practice.…”