Cholangiocytes: Cell transplantation

Abstract

Background: Due to significant limitations to the access to orthotropic liver transplantation, cell therapies for liver diseases have gained large interest worldwide.

Scope of review: To revise current literature dealing with cell therapy for liver diseases. We discussed the advantages and pitfalls of the different cell sources tested so far in clinical trials and the rationale underlying the potential benefits of transplantation of human biliary tree stem cells (hBTSCs).

Major conclusions: Transplantation of adult hepatocytes showed transient benefits but requires immune-suppression that is a major pitfall in patients with advanced liver diseases. Mesenchymal stem cells and hematopoietic stem cells transplanted into patients with liver diseases are not able to replace resident hepatocytes but rather they target autoimmune or inflammatory processes into the liver. Stem cells isolated from fetal or adult liver have been recently proposed as alternative cell sources for advanced liver cirrhosis and metabolic liver disease. We demonstrated the presence of multipotent cells expressing a variety of endodermal stem cell markers in (peri)-biliary glands of bile ducts in fetal or adult human tissues, and in crypts of gallbladder epithelium. In the first cirrhotic patients treated in our center with biliary tree stem cell therapy, we registered no adverse event but significant benefits.

General significance: The biliary tree stem cell could represent the ideal cell source for the cell therapy of liver diseases. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.

Keywords: Biliary tree stem cells; Grafting; Hepatic stem cells; Hepatocytes; Liver cell therapy; Mesenchymal stem cells.