Stem Cells: "A Journey into a New Frontier"

Bryon E. Petersen

Assistant Professor Dept. of Pathology P.O. Box 100275 University of Florida Gainesville, FL 32610

      Stem cells are defined as cells that are capable of self-renewal and are multi-potent, meaning they can differentiate into many specific cell types. Of the many adult stem cells described in the literature (hematopoietic, neural, hepatic, dermal, pancreatic and intestinal), it was once thought that these cells could only differentiate into the cell type from which they originated. It now appears that the adult stem cell is more plastic, versatile and capable of becoming many different types of cells (i.e. blood to brain & liver; brain to blood; liver to pancreas). Within the liver, activation, proliferation and differentiation of a distinct phenotype of cells, called oval cells, are observed after severe hepatic injuries in which the proliferation of existing hepatocytes is inhibited. Under these physiological conditions, oval "stem" cells can act as bipotential progenitors of the two types of epithelial cells within the liver, hepatocytes and bile ductular cells. Oval cells have been usually thought to be the progeny of a hepatic stem cell, native to the liver. Recently, however, we, as well as others have obtained clear evidence that in rodent models, hepatic oval cells, or at the least a fraction of them, can be derived from a precursor cell of bone marrow origin. The rodent data has been supported by recent findings that human bone marrow cells are capable of becoming hepatocytes and cholangiocytes as well. Having shown that oval "stem" cells can be derived from an extra-hepatic source we now have the technology to address many unanswered question in oval cell origin, fate and physiology through the use of sex mismatched bone marrow transplants. In addition, several laboratories including mine are showing hepatic oval cells can be induced to trans-differentiate into various cell types in both in vitro and in vivo conditions, demonstrating their versatility. It also appears that in the coming decade, the focus of research will be a stem cell-based therapy (or a combination of cell and gene therapy techniques). These new findings give the once lonely adult stem cell a new lease on life and perhaps a better chance in enabling both investigators and clinicians to fight life-threatening human diseases.