Adipose tissue-derived stem cells ameliorate hyperglycemia, insulin resistance and liver fibrosis in the type 2 diabetic rats

Abstract

BackgroundType 2 diabetes (T2D) is closely associated with liver fibrosis, but no effective treatments are currently available. This study was designed to investigate the therapeutic effects of ADSCs on insulin resistance, hyperglycemia, and liver fibrosis on T2D rats.MethodsWe first established a T2D rat model with liver fibrosis by using the combination of a high-fat diet (HFD), low-dose streptozotocin (STZ), and carbon tetrachloride (CCl4). Subsequently, the model rats were administrated by tail vein injection of PBS or ADSCs, respectively. Thereafter, insulin resistance and liver function were assessed by biochemical analysis, ELISA, histopathological examination, and q-PCR assay, respectively. Moreover, the molecular mechanisms of ADSCs on the effect of the TGF-β1/SMAD3 signaling pathway were further analyzed.ResultsOur data showed that ADSC transplantation significantly alleviated insulin resistance and hyperglycemia in the liver-injured T2D rats. We also found that ADSC transplantation could attenuate liver injury by improving liver function and inhibiting pathological changes of liver fibrosis, as well as through downregulation of TGF-β1 and phosphorylated SMAD3 both in vitro and in vivo.ConclusionsThese findings suggested that ADSC transplantation can ameliorate insulin resistance, hyperglycemia, and liver fibrosis via suppressing TGF-β1/SMAD3 signaling, which may provide a potential treatment strategy for liver fibrosis of T2D.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0743-7) contains supplementary material, which is available to authorized users.

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

“…Isolation of ADSCs was performed according to our previous reports [2][3][4]. Brie y, subcutaneous fat tissues were collected from the groin area of male C57BL/6 mice (n=10), and then cut into about 0.1mm 3 size and digested with 0.1% type I collagenase (Sigma-Aldrich, USA) in HBSS (Hyclone, USA) at 37 °C for 1 h. Afterwards, the digestive solutions were neutralized by α-MEM (Hyclone, USA) containing 20%FBS (Gibco, USA), ltered through a 100-μm cell strainer, followed by eliminating the red blood cells with osmotic lysates (Biyuntian Biological Co., Ltd., Shanghai, China).…”

“…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.…”

“…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

“…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 preclinical 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].…”

Transplantation of brown adipose tissue up-regulates miR-99a to ameliorate liver metabolic disorders in diabetic mice by targeting NOX4

“…Moreover, BAT is an important endocrine organ that secretes a variety of adipokines [12] and miRNAs [13] involved in systemic metabolic regulation, and the latter are involved in the regulation of a variety of biological processes and metabolic homoeostasis, including lipid metabolism, inflammation, oxidative stress, etc. Recent studies have found that transplantation of adipose tissue-derived stem cells (ADSCs) can significantly improve NAFLD and related liver fibrosis and cirrhosis in the rat or mouse model [14][15][16][17]. And the study has shown that BAT transplantation can improve glucose tolerance, increased insulin sensitivity, lower body weight, decreased fat mass and a complete reversal of high-fat diet (HFD)-induced insulin resistance in mice [18].…”