Hepatocyte transplantation improves survival in mice with liver toxicity induced by hepatic overexpression of Mad1 transcription factor

Hepatic overexpression of Mad1 with an adenoviral vector, AdMad, induced li ver toxicity in immunodeficient mice. Transduction of cultured hepatocytes with AdMad inhibited cellular DNA synthesis and cell cycling, along with in creased lactate dehydrogenase release, indicating cytotoxicity. When dipept idyl peptidase IV-deficient F344 rat hepatocytes were transplanted into the liver of immunodeficient mice after treatment with AdMad, significant port ions of the liver were repopulated. This was in agreement with correspondin g losses of host hepatocytes, which showed increased apoptosis rates. Morta lity in mice following AdMad treatment decreased significantly when animals were subjected to hepatocyte transplantation. The findings indicated that Mad1 overexpression perturbed hepatocyte survival. Investigation of pathoph ysiological mechanisms concerning specific cell cycle regulators in acute l iver toxicity will thus be appropriate. Cell therapy has potential for trea ting acute liver injury under suitable circumstances.