Chapter 97: Cellular Therapy, Tissue Engineering, and Artificial Liver Support

INTRODUCTION

Liver failure is ultimately treated by liver transplantation, but a huge gap exists between the availability and demand for donor livers. To help mitigate this imbalance, alternatives to liver transplantation are the subject of extensive research. These alternatives aim to serve either as short-term solutions (bridges to liver transplantation) or as more definitive measures to replace hepatic function and/or stimulate hepatic regeneration and recovery.

HEPATOCYTE TRANSPLANTATION

• Hepatocyte transplantation is a proposed alternative to whole-organ transplantation.¹

• Hepatocyte transplantation may lead to a restoration of liver function without organ transplantation, or it may serve as a means of prolonging life before liver transplantation becomes necessary for survival.¹

• It is an alternative to orthotropic liver transplantation (OLT).²

• The ability to receive an organ donation is not affected by hepatocyte transplantation.³

• The native liver is able to remain in place with hepatocyte transplantation.⁴

• Adult hepatocytes are preferred but are limited in availability, are difficult to isolate, propagate poorly, and undergo rapid functional deterioration in vitro.⁵

Indications

• Patients with metabolic diseases affecting the liver, which do not lead to cirrhosis (damaged hepatic architecture in cirrhosis, and some chronic liver diseases prevent engraftment of transplanted hepatocytes).³

• Patients with acute liver failure, with the aim of bridging the time gap prior to OLT; however, the results have not been too promising.^3,6

Technique

Step 1: Isolation of hepatocytes for transplantation:

• Hepatocytes are isolated from organs that have been rejected for liver transplantation.

• Adult hepatocytes (Fig. 97-1) are the preferred cell sources, but other sources for hepatocytes may include embryonic stem cells, hepatoblasts and fetal liver progenitor cells, endogenous liver stem cells, and bone marrow stem cells.

• Collagenase is used to digest the liver during the process of hepatocyte isolation.

Step 2: Implantation/infusion:

• Once the cells are isolated, the hepatocytes are transplanted by infusion through the portal vein using a perfusion pump.

• The number of hepatocytes that can be transported is determined by portal vein pressure.

• The site of transplantation is through the portal vein, directly to the liver.

• Ectopic sites of transplantation include the kidney capsule, peritoneal cavity, etc.

Step 3: Hepatocyte engraftment:

• How the hepatocytes interact with the environment after transplantation is most important for survival and function.

• Administration of growth factors can accelerate hepatocyte engraftment.

Step 4: Immunosuppression:

• Necessary to prevent immune-mediated rejection of transplanted hepatocytes.

• Optimal immunosuppressive regimens are still a concern and have yet to be determined.

• Few reliable methods exist to track cell engraftment and monitor rejection.

Conclusion

• Successful hepatocyte transplantation depends on finding ...