American Scientist

Liver Stem Cells. Stewart Sell and Zoran Ilic. 349 pp. Chapman and Hall/Landes Bioscience, 1997. $89.95.

Stem cells are essential elements of rapidly turning-over cell populations, required to maintain the supply of short-lived, differentiated cells. Stem cells have often been thought to be limited to tissues composed of these short-lived cells, but recent studies indicate that the liver and other tissues composed of long-lived cells that undergo little turnover may also contain stem-like cells. However, the roles and even the existence of liver stem cells continue to be controversial despite mounting evidence of their presence. In this setting, Stewart Sell and Zoran Ilic have performed a valuable service, providing an excellent general review of the literature pertaining to stem cells' role in the development and maintenance of the liver. References, more than 2,000 of them, are mostly derived from studies in rodents, reflecting the fact that most of the pertinent research has been carried out in rats and mice.

The text strongly emphasizes the analysis of tissue reactions that occur in vivo during the development of liver cancer as evidence for liver stem cells. Although the reader learns much about the complex multicellular nature of the tissue aberrations that precede the appearance of liver cancer in both experimental animals and humans, the massive amount of data reviewed ultimately fails to provide a clear and decisive answer to the question of whether cancer develops through a process of arrested differentiation and transformation of stem cells or from the dedifferentiation and transformation of mature cells. A definitive answer to the origin and nature of liver stem cells is very likely not possible from studies on development of liver cancer in intact organisms, either rodents or humans, because of the extreme complexity of the cellular alterations that transpire. The authors emphasize studies that have used antibodies to identify and trace the lineage of cells involved in cancer. The major problem with many of these antibody markers is the still-unanswered question of whether they truly indicate the lineage of a cell.

Analysis of lineage development following bone marrow transplantation led to great advances in characterizing bone-marrow stem cells and their lineages, insights into bone-marrow diseases and the therapeutic transplantation of bone marrow. Further application of liver stem-cell isolation and transplantation to investigate lineage development should lead to the more detailed characterization of liver stem cells, using studies patterned on the bone-marrow model.

Even when the existence of liver stem cells is well accepted and the cells themselves are fully characterized, the question of their role(s) in this normally static cell population will remain because liver stem cells do not appear to be needed for lineage renewal. Could liver stem cells have functions other than recharging cell lineages? Liver stem-like cells are veritable cytokine and growth-factor minifactories, producing multiple potent growth-mediating molecules. Could it be that liver stem cells serve important tissue regulatory roles in addition to, or instead of, lineage establishment? It seems certain that liver stem cells will be a continuing prime topic of research and scientific debate. For those readers who want to learn about liver stem cells, this book is an excellent place to start.—Joe W. Grisham, Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill