Human Umbilical Cord-Derived Mesenchymal Stem Cell Therapy Ameliorates Nonalcoholic Fatty Liver Disease in Obese Type 2 Diabetic Mice

Abstract

Nonalcoholic fatty liver disease (NAFLD) is increasingly common among patients with type 2 diabetes mellitus (T2DM). The two conditions can act synergistically to produce adverse outcomes. However, the therapeutic options for patients with NAFLD and T2DM are currently limited. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) have shown therapeutic potential for diabetes and hepatic disorders such as liver cirrhosis and fulminant hepatic failure. The present study is aimed at investigating the effect of human UC-MSCs on a mouse model of NAFLD and T2DM, characterized by obesity-induced hyperglycaemia, dyslipidaemia, hepatic steatosis, and liver dysfunction. Thirty-week-old male C57BL/6 db/db mice were infused with human UC-MSCs or phosphate-buffered saline (PBS) via the tail vein once a week for six weeks. Age-matched male C57BL/6 wild-type db/+ mice were used as controls. Body weight and random blood glucose were measured every week. One week after the sixth infusion, intraperitoneal glucose tolerance tests and insulin tolerance tests were performed and the blood and liver were harvested for biochemical and histopathological examinations. Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR), immunofluorescence staining, and western blot were performed to monitor the expression of the lipid metabolism- and regulatory pathway-related genes. UC-MSC infusions significantly ameliorated hyperglycaemia, attenuated the elevation of hepatic transaminases, and decreased lipid contents, including triglyceride, total cholesterol, and low-density lipoprotein cholesterol. Moreover, histological lesions in the liver diminished markedly, as evidenced by reduced lipid accumulation and attenuated hepatic steatosis. Mechanistically, UC-MSCs were found to regulate lipid metabolism by increasing the expression of fatty acid oxidation-related genes and inhibiting the expression of lipogenesis-related genes, which were associated with the upregulation of the HNF4α-CES2 pathway. Our results demonstrate that human UC-MSCs can ameliorate NAFLD and reverse metabolic syndrome in db/db mice. Thus, UC-MSCs may serve as a novel therapeutic agent for T2DM patients with NAFLD.

[Retracted] Antioxidative Capacity of Liver‐ and Adipose‐Derived Mesenchymal Stem Cell‐Conditioned Media and Their Applicability in Treatment of Type 2 Diabetic Rats

“…We observed that not only did the liver and adipose MSC-CM therapy have apparent improvement in levels of blood glucose, HbA1c, and AGEs but also the enhanced lipid panel (cholesterol, TG, LDL, HDL, and total lipids); renal function (urea, uric acid, creatinine, and total protein); liver function (AST, ALT, ALP, bilirubin, and albumin); CPK; C-peptide; HO-1; inflammatory markers including IL-6, TNF- α , and CRP; growth factors (liver and serum IGF-1); amylase; histopathological changes; pancreatic cell oxidative stress; and antioxidant markers (MDA, GSH, ROS, CAT, SOD, HO-1, and XO) toward the normal levels consequently reduce DM complications. These results are in agreement with the previous findings in [ 43 , 44 ]. Furthermore, the histopathological examination showed regeneration of β cells with the near-normal pancreatic islet architecture and a decrease in the necrotic score as shown in Figures 2(d) – 2(f) , which approved the therapeutic effect of both liver and adipose MSC-CM therapies with significant improvement in the case of liver MSC-CM than adipose MSC-CM therapy.…”

RETRACTED ARTICLE: Mesenchymal stem cell-derived exosomes exert ameliorative effects in type 2 diabetes by improving hepatic glucose and lipid metabolism via enhancing autophagy

“…diseases [30][31][32]. MSCs can be derived from different sources, such as umbilical cord, bone marrow, adipose tissue, skeletal muscle, liver, lung, and dermal tissues, etc.…”

Clinical Efficacy and Safety of Mesenchymal Stem Cells for Systemic Lupus Erythematosus

“…Cell therapy has become an attractive therapeutic strategy for various types of diseases [17][18][19][20], and it has achieved certain curative effects in induction therapy in patients with SLE [13]. The purpose of this study was to evaluate the efficacy of MSCs in the treatment of SLE by meta-analysis.…”