Advantages of adipose tissue stem cells over CD34+ mobilization to decrease hepatic fibrosis in Wistar rats

For hepatic failure, stem cell transplantation has been chosen as an alternative therapy, especially for mesenchymal stem cells (MSCs). The aim of this study was to investigate the effect of eugenol (EUG) on the in vivo antifibrotic activity of adipose tissue-derived MSCs (AT-MSCs) and the underlying mechanism. After characterization of MSCs, rats were divided into five groups, Group 1 (normal control), Group 2 (CCl4), Group 3 (CCl4 + AT-MSCs), Group 4 (CCl4 + EUG) and Group 5 (CCl4 + AT-MSCs + EUG). Biochemical and histopathological investigations were performed. Furthermore, expression of type 1 collagen, α-SMA, TGF-β1, Smad3 and P-Smad3 was estimated. Compared to the single treatment with AT-MSCs, the combination treatment of the fibrotic rats with AT-MSCs and EUG significantly improved the plasma fibrinogen concentration, IL-10 level and proliferating cell nuclear antigen expression, and also significantly decreased the serum levels of liver enzymes, IL-6, IL-1β, TNF-α, type III collagen, hyaluronic acid, hydroxyproline and the TGF-β growth factor. Furthermore, the combination treatment significantly decreased the hepatic expression of fibrotic markers genes (Type 1 collagen and α-SMA) and proteins (α-SMA, TGF-β1 and phospho-Smad3) more than the treatment with AT-MSCs alone. We demonstrated that the combination treatment with EUG and AT-MSCs strongly inhibited the advancement of CCl4-induced hepatic fibrosis, compared with AT-MSCs alone, through TGF-β/Smad pathway inhibition. This approach is completely novel, so more investigations are necessary to improve our perception of the underlying molecular mechanisms accountable for the effects of EUG on the antifibrotic potential of AT-MSCs.

Section: Isolation Culture and Characterization Of At-mscsmentioning

confidence: 99%

AT-MSCs Antifibrotic Activity is Improved by Eugenol through Modulation of TGF-β/Smad Signaling Pathway in Rats

et al. 2020

“…All previous studies have been used stem cells derived from bone marrow [ 15 , 20 ], umbilical cord [ 21 ] the liver itself [ 22 ] or hepatic cell line [ 23 ] and the amniotic membrane [ 16 ], but in this study we used mesenteric adipose tissue to harvest stem cells and applied a modified technique which proved good results clinically and histopathologically. Few animal studies administered adipose stem cells (ADSC) for hepatic regeneration with different methods [ 24 , 25 ]. Sakai et al also enrolled a clinical trial in 2017 based on intrahepatic arterial infusion of autologous subcutaneous adipose tissue stem cells for liver cirrhosis, but it is not completed yet [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Regenerative effect of mesenteric fat stem cells on ccl4-induced liver cirrhosis, an experimental study

Haghani

Annals of Medicine and Surgery

et al. 2020

Background Liver cirrhosis is a chronic disease in which normal liver tissue is replaced by fibrous tissue, leads to liver malfunction. Although transplantation is the most certain cure, stem cell therapies are shedding light on efforts to regenerate cirrhotic liver. The purpose of this study was to evaluate the regenerative potential of mesenteric fat stem cells in CCL4-induced liver cirrhosis in an animal model. Methods Thirty rats were treated with the mixture of CCL4 and olive oil intraperitoneally by a dose of 0.2 ml (0.1 ml CCL4 and 0.1 ml olive oil) every other day for 16 weeks till cirrhosis signs appeared. Fifteen rats were randomly selected as control group. Others treated by mesenteric fat derived mesenchymal stem cells transferred into the liver parenchyma. Results After 5 weeks, rats received stem cells had improved clinically by increased movements, appetite, improvement in overall behavior and decreased abdomen size. Histopathologically, liver cells showed state of regeneration and forming new colonies. Conclusion Liver cirrhosis was induced. The mesenchymal stem cells derived from mesenteric adipose tissue could improve hepatic status of the rats, as cirrhotic livers were regenerated back into normal appearing parenchyma. Rats’ clinical behavior also reached healthy status.

“…All previous studies have been used stem cells derived from bone marrow (15,20), umbilical cord (21) the liver itself (22) or hepatic cell line (23) and the amniotic membrane (16), but in this study we used mesenteric adipose tissue to harvest stem cells and applied a modi ed technique which proved good results clinically and histopathologically. Few animal studies administered adipose stem cells (ADSC) for hepatic regeneration with different methods (24,25). Sakai etal.…”

Section: Discussionmentioning

confidence: 99%

Regenerative Effect of Mesenteric Fat Stem Cells on ccl4-Induced Liver Cirrhosis

Haghani

et al. 2020

Preprint

Abstract Background: Liver cirrhosis is a chronic disease in which normal liver tissue is replaced by fibrous tissue, leads to liver malfunction. Although transplantation is the most certain cure, stem cell therapies are shedding light on efforts to regenerate cirrhotic liver. The purpose of this study was to evaluate the regenerative potential of mesenteric fat stem cells in CCL4-induced liver cirrhosis in an animal model.Methods: Thirty rats were treated with the mixture of CCL4 and olive oil intraperitoneally by a dose of 0.2 ml (0.1 ml CCL4 and 0.1 ml olive oil) every other day for 16 weeks till cirrhosis signs appeared. Fifteen rats were randomly selected as control group. Others treated by mesenteric fat derived mesenchymal stem cells transferred into the liver parenchyma.Results: After 5 weeks, rats received stem cells had improved clinically by increased movements, appetite, improvement in overall behavior and decreased abdomen size. Histopathologically, liver cells showed state of regeneration and forming new colonies.Conclusion: Liver cirrhosis was induced successfully. The mesenchymal stem cells derived from mesenteric adipose tissue could improve hepatic status, as cirrhotic livers were regenerated back into normal parenchyma. Rats’ clinical behavior also reached healthy status.