An in vitro model of cell transplantation for evaluation of cell engraftment enhancers

The limited availability of organs for liver transplantation has focused interest on the use of cell transplants to restore hepatic function. Advances have been made in rodent models, but efficacy is limited in humans due to low engraftment efficiency. In rodents, pretransplantation treatment of the liver with engraftment enhancers (EE) shows that repopulation is feasible, although the toxicity of the substances impedes their application in humans. Evaluation of low-toxicity engraftment enhancers for human use requires testing in animal models, a time-consuming, expensive process that also raises ethical issues. To reduce animal use in the preliminary evaluation of a new EE, we designed an easily quantitated in vitro method that mimics an intraportal cell transplant. It is based on EE-mediated disruption of intercellular adhesion in confluent endothelial cell cultures.