Transplantation of Stem Cell-Derived Hepatocytes in Patients with End-Stage Liver Diseases

Liver disease constitutes a major cause of mortality and morbidity worldwide. Although liver transplantation offers a potential and definitive cure to many patients, the shortage of donor organs, complexity and risks of surgical procedure result in many patients not qualifying for liver transplantation or dying while on the waiting list.Over the last decade, much effort was spent in exploring the use of hepatocyte transplantation to replace the diseased liver as a simpler and less invasive treatment modality. While there were measurable improvements in liver function and correction of metabolic defects, the therapeutic effect is short-lived and limited. The primary factor limiting the advancement of this approach is the lack of good-quality hepatocytes. This unmet clinical need has thus fuelled the intense search for liver stem cell as a cell source that can generate limitless supply of useful cells for therapeutic purposes.These stem cells or their differentiated hepatocyte progenies, harvested in environment conforming to good manufacturing practice (GMP) guidelines and free of zoonotic infection risks, can then be cryopreserved in cell banks, allowing immediate access when the cells are needed urgently. They can be transplanted into patients with acute and chronic liver insufficiency, as gene therapy in metabolic diseases, as well as for populating a bioreactor for bioartificial liver dialysis.The promise of liver stem cells lies in their ability to continuously generate unlimited supply of stem cells or derived hepatocytes. Current understanding and use of liver stem cells is still in its infancy stage of development. Stem cell derived hepatocytes must be comparable to adult hepatocytes in both numbers and quality such that they are clinically useful. Currently, the procedure of hepatocytes transplantation may be considered as a bridging therapy until organ transplantation becomes available or to reverse a decompensated cirrhosis to a compensated one.