Intrahepatic transplantation of adipose-derived stem cells attenuates the progression of non-alcoholic fatty liver disease in rats

Abstract

Non‑alcoholic fatty liver disease (NAFLD) is one of the major causes of chronic liver injury affecting the general health of various populations. In the present study, adipose tissue‑derived stem cells (ADSCs), which were isolated from the adipose tissues of Sprague‑Dawley rats, were transplanted into the liver of high‑fat‑diet‑induced NAFLD rats via the portal vein to attenuate the disease progression of NAFLD. The results demonstrated that ADSC transplantation reduced the serum levels of alanine aminotransferase, total bilirubin, total cholesterol, triglycerides and fatty acids, and reduced the content of malondialdehyde in the liver homogenates. By contrast, ADSC transplantation caused a significant increase in superoxide dismutase activity. These data suggested that the ADSC transplantation improved the liver function, and reduced lipid metabolism and oxidative stress. In addition, the hepatic pathological changes were decelerated, lipid accumulation was reduced, and serum levels of the pro‑inflammatory factors, tumor necrosis factor‑α and interleukin‑6, were downregulated by the ADSC transplantation. Taken together, transplantation with ADSCs attenuates the disease progression of high‑fat‑diet induced NAFLD, therefore, may offer a potential therapeutic approach for the treatment of NAFLD.

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].…”

Cell therapy in chronic liver disease

“…In fact, bone marrow-derived CD45 cells have been suggested to be superior candidates to adipose tissue-derived MSCs for the treatment of liver cirrhosis due to their higher capacity for structural and functional improvement of a CCl4-induced fibrotic liver mouse model (37). Intrahepatic transplantation of adipose tissue-derived stem cells has also been proposed as a therapeutic approach for the treatment of NAFLD, as it may reduce lipid metabolism and oxidative stress, as well as improve liver function (38). A phase I/IIa clinical trial testing intrahepatic injection of these cells for the treatment of cirrhosis will begin shortly (39).…”

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].…”