Adipose-Derived Stem Cells Can Abrogate Chemical-Induced Liver Fibrosis and Facilitate Recovery of Liver Function

Abstract

Adipose-derived stem cells (ADSCs) are easy to harvest and have the ability for self-renewal and to differentiate into various cell types, including those of the hepatic lineage. Studies on the use of ADSCs for liver transplantation are, however, limited. The objective of this study was to investigate the feasibility of using human ADSCs and to better understand their mechanism of action for the repair of liver damage in a thioacetamide (TAA)-induced model of chronic liver damage in the rat. To induce liver damage, 200 mg/kg TAA was injected intraperitoneally into Wistar rats every 3 days for 60 days. For cell therapy, 1 × 10 6 human ADSCs suspended in 300 ml of phosphate-buffered saline were transplanted into each experimental rat by direct liver injection. Immunohistochemistry showed that the transplanted ADSCs differentiated into albumin-and a-fetoproteinsecreting liver-like cells 1 week after transplantation. In addition, liver function recovered significantly, as determined by biochemical analyses that analyzed total bilirubin, prothrombin time, and albumin levels. The Metavir score, derived from histopathological analysis, also showed a significant decrease in liver fibrosis and inflammatory activity after ADSC transplantation. Finally, we found a reduction in the expression of a-smooth muscle actin, a marker of hepatic stellate cells, which produce collagen fiber, and an increase in the expression of matrix metalloproteinase-9, which degrades collagen fiber, after ADSC transplantation. These findings are consistent with abrogation of liver fibrosis in the ADSC therapy group. Consequently, these results suggest that ADSC transplantation may facilitate recovery from chronic liver damage and thus may have clinical applications.

Adipose-Derived Stem Cells in Tissue Regeneration: A Review

“…However, this study is unable to confirm differentiation at the functional level. In contrast, human ASCs induced toward the hepatocyte lineage and directly injected into models of liver fibrosis are found to secrete albumin and -fetoprotein, decrease fibrosis and inflammation and improve liver function [256]. Similarly, induced human ASCs transplanted into CCl 4 -injured livers in nude mice not only increase their production of albumin protein but also restore liver functions such as ammonia and purine metabolism and decrease liver injury markers, such as alanine aminotransferase and aspartate aminotransferase activity [159].…”

Symptomatic knee osteoarthritis treatment using autologous adipose derived stem cells and platelet-rich plasma: a clinical study

“…To date, ADSCs have become excellent candidates for research and clinical applications. Many studies have shown that ADSC transplantation efficiently improved almost all symptoms of certain diseases, such as liver fibrosis (Harn et al, 2012), nerve defects (Gu et al, 2012;Liu et al, 2011;Santiago et al, 2009), ischemia (Mazo et al, 2012;Rigol et al, 2010), skeletal muscle injury (Pecanha et al, 2012), passive chronic immune thrombocytopenia (Xiao et al, 2012), and myocardial infarction (Yang et al, 2012) in animals, and systemic sclerosis in humans (Riordan et al, 2009;Scuderi et al, 2013).…”

Inhibition of penile tunica albuginea myofibroblasts activity by adipose‑derived stem cells

“…Otherwise, ADSCs could degrade collagen fiber by increasing the expression of matrix metalloproteinase-9. Therefore, ADSCs could abrogate chemical-induced liver fibrosis (32). Moreover, after ADSC or CM-ADSCs injected to scars, Zhang Q confirmed that the regular collagen architecture was recovered and that the expression of αSMA and collagen type Ι were also decreased by histomorphometric and real-time quantitative polymerase chain reaction analysis (33).…”