Improving the Techniques for Human Hepatocyte Transplantation: Report from a Consensus Meeting in London

Abstract

On September 6 and 7, 2009 a meeting was held in London to identify and discuss what are perceived to be current roadblocks to effective hepatocyte transplantation as it is currently practiced in the clinics and, where possible, to offer suggestions to overcome the blocks and improve the outcomes for this cellular therapy. Present were representatives of most of the active clinical hepatocyte transplant programs along with other scientists who have contributed substantial basic research to this field. Over the 2-day sessions based on the experience of the participants, numerous roadblocks or challenges were identified, including the source of cells for the transplants and problems with tracking cells following transplantation. Much of the discussion was focused on methods to improve engraftment and proliferation of donor cells posttransplantation. The group concluded that, for now, parenchymal hepatocytes isolated from donor livers remain the best cell source for transplantation. It was reported that investigations with other cell sources, including stem cells, were at the preclinical and early clinical stages. Numerous methods to modulate the immune reaction and vascular changes that accompany hepatocyte transplantation were proposed. It was agreed that, to obtain sufficient levels of repopulation of liver with donor cells in patients with metabolic liver disease, some form of liver preconditioning would likely be required to enhance the engraftment and/or proliferation of donor cells. It was reported that clinical protocols for preconditioning by hepatic irradiation, portal vein embolization, and surgical resection had been developed and that clinical studies using these protocols would be initiated in the near future. Participants concluded that sharing information between the groups, including standard information concerning the quality and function of the transplanted cells prior to transplantation, clinical information on outcomes, and standard preconditioning protocols, would help move the field forward and was encouraged.

Construction of liver tissue in vivo with preparative partial hepatic irradiation and growth stimulus: investigations of less invasive techniques and progenitor cells

“…However, it has not been prevalent as a standard therapeutic option, mainly because of the limited number of hepatocytes at one time and the shortage of transplantable primary hepatocytes (4,22). To overcome these hurdles, the methods for growth of transplanted hepatocytes in the recipient, or the development or availability of substitute for primary hepatocytes, such as xenogeneic hepatocytes, fetal hepatocytes, and hepatic stem cells/progenitor cells have been explored.…”

“…Hepatocyte transplantation (HT) has been performed in both animal experiments and in patients with hepatic inherited disorders (1)(2)(3)(4). Because the number of hepatocytes transplanted safely at one time is limited due to the occurrence of portal hypertension, transplanted hepatocytes need to proliferate in the host liver to completely correct the underlying disorder (5,6).…”

Reprogrammed Cell?based Therapy for Liver Disease: From Lab to Clinic

“…The reason for this problem is that expansion and proliferation of transplanted cells need a tense sustain of hepatic cell mass (75). Furthermore, besides pluripotent stem cells-related problems, cell delivery complications are another important limiting factor of liver cell therapy.…”

The Liver Vascular Bed for Hepatocytes Cell Therapy and Tissue Engineering

“…New problems appeared when human studies were initiated, such as poor initial and long term engraftment and function. It was agreed in a recent consensus, that to obtain sufficient levels of repopulation of liver with donor cells in patients with metabolic liver disease, some form of liver preconditioning would be required to enhance the engraftment proliferation of donor cells (Puppi et al 2011). Therefore the switch from the animal model to human studies in the set up of acute hepatic failure is not direct and the amount of cells to be transplanted based on animal studies is probably irrelevant to humans.…”

“…clinical stages (Puppi et al 2011). Major problems do not allow this method to be practical and these include the shortage of organs for cell recruitment and limitations in cell preservation.…”