Hepatocyte transplantation in the treatment of acute liver failure: microencapsulated hepatocytes versus hepatocytes attached to an autologous biomatrix.
A liver transplant is considered today to be the only effective therapeutic solution for many otherwise intractable hepatic disorders. However, liver transplantation is beset by shortage of donors. Over the years, many liver support systems have been developed to supply the liver functions, mostly as a bridge to transplantation. Transplantation of isolated hepatocytes (HcTx) instead of whole liver has constituted one of the most appealing possibilities to treat several diseases. We compared two different models of HcTx in a surgical model of acute liver failure in pigs, using microencapsulated hepatocytes (MHcTx) and hepatocytes attached to a porcine biomatrix (PBMHcTx), both transplanted into peritoneum. The collected data were survival, laboratory findings, hemodynamic parameters, light microscopy, histology, MTT, and glycogen content. The group with PBMHcTx has a better outcome than the group with MHcTx (p < 0.05). Histology showed normal morphology of the hepatocytes, high glycogen content, 75% viability, positive MTT, and 95% adhesion of the hepatocytes to the biomatrix. Our biomatrix (PBM) provides cell-to-cell contact and interaction with extracellular matrix, which have been shown to play major roles in hepatocyte survival and physiologic regulation of gene expression, and guarantee a prompt engraftment and an adequate neovascularization. PBMHcTx is a useful method to treat acute liver failure and it indicates a possible liver-direct gene therapy in the treatment of inherited and acquired disorders.
Ambrosino
Giovanni
G
Department of Surgical and Gastroenterologic Sciences, Liver Transplant Unit, School of Medicine, University of Padova, Via Giustiniani 2, 35128 Padova, Italy. giovanni.ambrosino@unipd.it
Varotto
Sergio
S
Basso
Stefano M M
SM
Cecchetto
Attilio
A
Carraro
Paolo
P
Naso
Agostino
A
De Silvestro
Giustina
G
Plebani
Mario
M
Abatangelo
Giovanni
G
Donato
Daniele
D
Cestrone
Andriano
A
Giron
Gianpiero
G
D'Amico
Davide F
DF
D000818:Animals; D000831:Animals, Newborn; D001672:Biocompatible Materials / Q000494:pharmacology* / Q000627:therapeutic use; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004339:Drug Compounding / Q000379:methods*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology*; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D017114:Liver Failure, Acute / Q000628:therapy*; D008297:Male; D015996:Survival Rate; D034421:Sus scrofa; D016378:Tissue Transplantation / Q000379:methods*; D016896:Treatment Outcome
D001672:Biocompatible Materials; D006003:Glycogen