New concepts in liver regeneration

Abstract

The unique ability of the liver to regenerate itself has fascinated biologists for years and has made it the prototype for mammalian organ regeneration. Harnessing this process has great potential benefit in the treatment of liver failure and has been the focus of intense research over the past 50 years. Not only will detailed understanding of cell proliferation in response to injury be applicable to other dysfunction of organs, it may also shed light on how cancer develops in a cirrhotic liver, in which there is intense pressure on cells to regenerate. Advances in molecular techniques over the past few decades have led to the identification of many regulatory intermediates, and pushed us onto the verge of an explosive era in regenerative medicine. To date, more than 10 clinical trials have been reported in which augmented regeneration using progenitor cell therapy has been attempted in human patients. This review traces the path that has been taken over the last few decades in the study of liver regeneration, highlights new concepts in the field, and discusses the challenges that still stand between us and clinical therapy.

Figure 1. The Two Levels of Liver Regeneration

Figure 2. Cluster of Fetal Liver Progenitors

These cells have high nuclear-cytoplasmic ratio and are positive for EPCAM, CD44, CK19 and NCAM but negative for albumin, AFP and CK7. They are maintained on laminin extracellular matrix, mouse embryonic fibroblast feeder layers and kept in cultures with high dose FGF (unpublished data)