Clinical application of stem cells in liver diseases

Bae, Si Hyun

Abstract

Most liver diseases lead to hepatic dysfunction with organ failure. Liver transplantation is the best curative therapy, but it has some limitations such as donor shortage, possibility of rejection, and maintenance of immunosuppressant. New therapies have been actively searched for over several decades, primarily in the form of artificial liver support devices and hepatocyte transplantation, but both of these modalities remain experimental. Stem cells have recently shown promise in cell therapy because they have the capacity for self-renewal and multilineage differentiation, and are applicable to human diseases. Very recent reports of unexpected plasticity in adult bone marrow have raised hopes of stem cell therapy offering exciting therapeutic possibilities for patients with chronic liver disease. Both rodent and human embryonic stem cells, bone marrow hematopoietic stem cells, mesenchymal stem cells, umbilical cord blood cells, fetal liver progenitor cells, adult liver progenitor cells, and mature hepatocytes have been reported to be capable of self-renewal, giving rise to daughter hepatocytes both in vivo and in vitro. These cells can repopulate livers in animal models of liver injury and appear to be able to improve liver function. However, significant challenges still exist before these cells can be used in humans, such as the lack of consensus about the immunophenotype of liver progenitor cells, uncertainty of the physiological role of reported candidate stem/progenitor cells, practicality of obtaining sufficient quantity of cells for clinical use, and concerns over ethics, long-term efficacy, and safety. There have been reports of phase 1 trials using stem cell transplantation in humans for liver diseases, but more effective trials are needed. We review the use of stem cells (focusing on adult ones) and the reported human clinical trials, and highlight the challenges facing clinicians in their quest to use liver stem cells to save lives.