Serous Membrane Detachment with Ultrasonic Homogenizer Improves Engraftment of Fetal Liver to Liver Surface in a Rat Model of Cirrhosis.

Yumi Kawakatsu-Hatada,Hideki Taniguchi,Kodai Kimura,Soichiro Murata,Akihiro Mori

doi:10.3390/ijms222111589

Yumi Kawakatsu-Hatada, Hideki Taniguchi + Show 3 more

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https://doi.org/10.3390/ijms222111589

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Abstract

Liver transplantation is the most effective treatment for end-stage cirrhosis. However, due to serious donor shortages, new treatments to replace liver transplantation are sorely needed. Recent studies have focused on novel therapeutic methods using hepatocytes and induced pluripotent stem cells, we try hard to develop methods for transplanting these cells to the liver surface. In the present study, we evaluated several methods for their efficiency in the detachment of serous membrane covering the liver surface for transplantation to the liver surface. The liver surface of dipeptidyl peptidase IV (DPPIV)-deficient rats in a cirrhosis model was detached by various methods, and then fetal livers from DPPIV-positive rats were transplanted. We found that the engraftment rate and area as well as the liver function were improved in rats undergoing transplantation following serous membrane detachment with an ultrasonic homogenizer, which mimics the Cavitron Ultrasonic Surgical Aspirator® (CUSA), compared with no detachment. Furthermore, the bleeding amount was lower with the ultrasonic homogenizer method than with the needle and electric scalpel methods. These findings provide evidence that transplantation to the liver surface with serous membrane detachment using CUSA might contribute to the development of new treatments for cirrhosis using cells or tissues.

Highlights

Liver damage leads to the production of collagen fibers by activated stellate cells
We first tested our hypothesis that the serous membrane on the liver surface prevented the engraftment of transplanted fetal liver
While several studies have investigated that injection of stem cells into the hepatic artery artery or spleen as an alternative treatment [26,27,28], few studies have evaluated transplanor spleen as an alternative treatment [26,27,28], few studies have evaluated transplantation to tation to the liver surface

Summary

Introduction

Liver damage leads to the production of collagen fibers by activated stellate cells. During chronic liver damage, prolonged activation of stellate cells leads to the accumulation of collagen fibers produced by these cells in the liver, and the progression of ensuing fibrosis causes cirrhosis. The most common causes of cirrhosis are hepatitis B and C virus infections and alcoholic and nonalcoholic fatty liver disease [1]. Despite the decline in cirrhosis due to hepatitis B and C virus infections following the development of effective antiviral agents, the incidence rates of nonalcoholic fatty liver disease-related liver failure and hepatocellular carcinoma are increasing [2,3]. Nonalcoholic fatty liver disease is primarily caused by obesity and lifestyle-related diseases and, when left unresolved, advances to nonalcoholic steatohepatitis and cirrhosis and hepatocellular carcinoma [4].

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