Potential applications for cell regulatory factors in liver progenitor cell therapy.

ABSTRACT

Orthotopic liver transplant represent the state of the art treatment for terminal liver pathologies such as cirrhosis in adults and hemochromatosis in neonates. A limited supply of transplantable organs in relationship to the demand means that many patients will succumb to disease before an organ becomes available. One promising alternative to liver transplant is therapy based on the transplant of liver progenitor cells. These cells may be derived from the patient, expanded in vitro, and transplanted back to the diseased liver. Inborn metabolic disorders represent the most attractive target for liver progenitor cell therapy, as many of these disorders may be corrected by repopulation of only a portion of the liver by healthy cells. Another potential application for liver progenitor cell therapy is the seeding of bio-artificial liver matrix. These ex vivo bioreactors may someday be used to bridge critically ill patients to other treatments. Conferring a selective growth advantage to the progenitor cell population remains an obstacle to therapy development. Understanding the molecular signaling mechanisms and micro-environmental cues that govern liver progenitor cell phenotype may someday lead to strategies for providing this selective growth advantage. The discovery of a population of cells within the bone marrow possessing the ability to differentiate into hepatocytes may provide an easily accessible source of cells for liver therapies.