Systemic Treatment of Acute Liver Failure with Adipose Derived Stem Cells

ABSTRACT

Purpose of the study: The definitive treatment for liver failure is, currently, liver transplantation. Research into other possible treatments, focused on achieving regeneration of the liver parenchyma, have led to the development of methods to generate hepatocytes from stem cells. In our study, we transplant allogenic adipose-derived stem cells (ASCs), not previously differentiated to hepatocytes, to treat acute liver failure induced by intraperitoneal administration of carbon tetrachloride (CCl₄) in a Sprague-Dawley rat model. Material and Methods: The ASCs were delivered via the tail vein, having previously been labeled with PKH26, a fluorescent membrane marker. Two control groups were established, Group 1(n = 15) consisting of olive oil (5 mL/kg) and Group 2(n = 15): 1 × 10⁶ PKH26-labeled ASCs. Further, two study groups, Group 3(n = 30): CCl₄ dissolved in olive oil and Group 4(n = 30): CCl₄ dissolved in olive oil and 1 × 10⁶ PKH26-labeled ASCs completed the experimental design.Results: Blood samples were analyzed, finding AST and ALT levels significantly higher in treatment over control groups at 24 and 48 hours. The mortality rates were statistically different between control groups and Group 3 (Group 1-3 p = .04, Group 2-3 p = .04) and between Groups 3 and 4 (p = .02). Examining the liver parenchyma, a significantly higher number of ASCs were observed in Group 4 than in Group 2 at all time points (p = .00). Conclusions: The intravenous injection of allogenic ASCs in this model of CCl₄-induced liver failure reduced the mortality in treated animals. ASCs injected in the rat tail vein were found in the liver in animals with induced acute liver failure.

Keywords: :

• adult stem cells
• mesenchymal stem cells
• liver transplant
• liver failure
• fulminant liver failure

ABBREVIATIONS
MSCs	=	Mesenchymal stem cells
ASCs	=	Adipose derived stem cells
CCl4	=	Carbon tetrachloride
AST	=	Aspartate aminotransferase
ALT	=	Alanine aminotransferase

ACKNOWLEDGMENTS

We are grateful to Rosario Madero, Head of the Biostatistics Unit of La Paz University Hospital for her help with the design and statistical analysis for this study. We would also like to thank Mr. David Bruhn for his assistance in correcting the manuscript to a more readable form.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This study was supported by a Fundación Mutua Madrileña grant.