Researchers Convert Cirrhosis-Causing Cells to Healthy Liver Cells in Mice

UCSF News reports on the research of the Willenbring Lab and others demonstrating in mice that healthy new liver cells could be generated within the organ itself, thus making engraftment unnecessary. The article noted that the very cells that drive liver disease were converted, thereby reducing liver damage and improving liver function simultaneously. The study was recently reported on in a paper published by the journal Cell Stem Cell. 

Advances in stem cell research have made it possible to convert patients’ skin cells into heart cells, kidney cells, liver cells and more in the lab dish, giving researchers hope that one day such cells could replace organ transplantation for patients with organ failure. But successfully grafting these cells into patients’ failing organs remains a major clinical challenge.

Now a team of researchers led by UC San Francisco scientists has demonstrated in mice that it is possible to generate healthy new liver cells within the organ itself, making engraftment unnecessary. What’s more, they did it by converting the very cells that drive liver disease, thereby reducing liver damage and improving liver function at the same time. The technique takes advantage of a viral gene delivery technology that has gone through early validation in patients for liver-directed gene therapies, suggesting it could be readily translated into a therapy for patients with liver disease, said Holger Willenbring, MD, PhD, a professor of surgery at UCSF and senior author of the new study, published June 2, 2016, in the journal Cell Stem Cell.

“Part of why this works is that the liver is a naturally regenerative organ, so it can deal with new cells very well. What we see is that the converted cells are not only functionally integrated in the liver tissue, but also divide and expand, leading to patches of new liver tissue,” said Willenbring, who is also associate director of the Liver Center at UCSF and a member of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research.

Co-lead authors were Milad Rezvani, MD, and Regina Español-Suñer, PhD, of UCSF. Other UCSF authors include Yann Malato, PhD, Laure Dumont, Andrew A. Grimm, MD, PhD, Julia G. Bindman, Bernadette Y. Hsu, Syed J. Naqvi, MD, and Carlos U. Corvera, MD, of UCSF. Other authors were Eike Kienle, PhD, and Ellen Wiedtke in Grimm ‘s lab at the University of Heidelberg Hospital, and Robert F. Schwabe, MD, of Columbia University.