Transplantation of Hepatocytes for Treatment of Surgically Induced Acute Hepatic Failure in the Rat

Abstract

Efficacy of transplanted hepatocytes was evaluated in rats with a surgically induced acute hepatic failure. After 75% liver resection and portacaval shunt, the intrasplenic or intraperitoneal injection of 20 million isolated fresh hepatocytes was shown to significantly reduce the mortality rate. These results confirm that the transplantation of isolated hepatocytes may prevent death in rats with acute hepatic failure, and suggest that hepatocyte transplantation acts by a mechanism of hepatic support.

A Predictable Pathophysiological Model of Porcine Hepatic Failure

“…portacaval shunt with irreversible arterial ischaemia as described by De Groot ct al. [6] or the partial hepatectomy technique of Minato et al [ 16], The present model is theoret ically reversible because the damaged liver remains in the circulation and both insults are of a sublethal nature (the dose of CCU as described by van Leenhoff et al [25] and the arterial ischaemia chosen from the experi ence of Kahn et al [13]). In further prelimi nary studies, the administration of PGF2a rcsuted in survival in about 40% of ani mals, thus confirming the possibility of re versibility.…”

In vivo Dynamic ^99mTc-HIDA Scintigraphy after Hepatocyte Transplantation: A New Method for the Monitoring of Graft Function

“…Although expected, this negative finding was of importance, since the nidation of isolated hepatocytes in the lung has been described after HTX [14,19]. Apparently, overflow of single cells from the portal circulation through the caval route into the pulmonary vascular bed can occur.…”

“…The potential thera peutic consequences of this relatively new transplantation technique have not gone un noticed: HTX has been applied in the treat ment of enzyme deficiency disease [7,13,20,24,25], acute liver failure [2,12,14,21,22] and drug-induced cirrhosis [5] in several ani mal models with varying degrees of success. All investigators in this field used postmor tem histological examination as the most important parameter for graft survival.…”

Hepatocyte transplantation

“…The acute hepatic failure model has been used mainly for small animals. 18, 33 Although support of the anhepatic host is the ultimate test of the efficacy of transplanted hepatocytes, in reality the model is difficult because (1) agents used to chemically induce acute hepatic failure may damage transplanted hepatocytes; (2) transplanted hepatocytes may require some time to establish themselves functionally; and (3) the mass of transplanted hepatocytes may not be sufficient to provide full liver support. In addition, there have been conflicting reports regarding the beneficial effects of the hepatocytes themselves versus the provision of metabolic support of the hosts until recovery is possible.12J6s18…”