Coencapsulation of hepatocytes with bone marrow mesenchymal stem cells improves hepatocyte-specific functions.
BACKGROUND
Hepatocyte transplantation is an alternative to liver transplantation, which is hampered by short survival time and immunorejection. In this study, we investigated the specific functions of hepatocytes coencapsulated with bone marrow mesenchymal stem cells (MSCs) in vitro, and we further examined whether transplantation of coencapsulated hepatocytes and MSCs could enhance the ability of hepatocytes to alleviate acute liver failure in vivo.


METHODS
Rat hepatocytes and MSCs were isolated and coencapsulated by alginate-poly-l-lysine-alginate microencapsulation. Cell functions were monitored during the course of cell culturing. Acute liver failure in rats was induced by d-galactosamine administration. These rats were subjected to intraperitoneal transplantation of coencapsulated hepatocytes with MSCs, encapsulated hepatocytes alone, or empty vehicles after 24 hr. The survival rate and liver functions were assessed. Immunofluorescence microscopy was used for the analysis of coencapsulated cells before and 7 days after transplantation.


RESULTS
Hepatocyte-specific functions, including albumin secretion and urea synthesis, were all significantly improved in the coencapsulation group compared with the encapsulated hepatocytes group (P<0.05). Similar trend was observed for cell cycle analysis of hepatocytes. Intraperitoneal transplantation of coencapsulated hepatocytes with MSCs not only increased the survival rate but also improved liver functions in a rat model of acute liver failure. Some MSCs transdifferentiated into hepatocyte-like cells in vivo, which expressed albumin, a typical marker of hepatocyte.


CONCLUSIONS
Encapsulation of hepatocytes and MSCs improved hepatocyte-specific functions in vitro and in vivo. Transplantation of coencapsulated hepatocytes and MSC might be a promising strategy for cell-based therapy for acute liver diseases.
Shi
Xiao-Lei
XL
Department of Hepatobiliary Surgery, The Affiliated DrumTower Hospital of Nanjing University Medical School, Nanjing, China.
Zhang
Yue
Y
Gu
Jin-Yang
JY
Ding
Yi-Tao
YT
D000818:Animals; D051381:Rats; D000208:Acute Disease; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D018929:Cell Culture Techniques / Q000379:methods; D002453:Cell Cycle / Q000502:physiology; D004195:Disease Models, Animal; D005269:Femur; D022781:Hepatocytes / Q000166:cytology / Q000473:pathology / Q000502:physiology / Q000637:transplantation; D017093:Liver Failure / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008111:Liver Function Tests; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology; D017207:Rats, Sprague-Dawley; D015996:Survival Rate