Liver disease and regeneration
The Mission of the Program of liver disease and regeneration
The mission of the Program led by Valerie Gouon-Evans is to decipher the mechanisms that drive liver development and disease in order to ultimately discover new regenerative liver therapies. The Program at the CReM involves research scientists and physician scientists working together with clinicians from the Boston Medical Center (BMC) Section of Gastroenterology, the Boston University (BU) Amyloid Treatment and Research Program, and the BU/BMC Alpha-1 Center. The Program’s best known foci to date have been on the monogenetic chronic liver diseases associated with familial amyloidosis, alpha-1 antitrypsin deficiency, or hemochromatosis in addition to non-genetic related acute and chronic liver diseases, including cirrhosis.Liver transplantation is currently the only treatment for liver failure. Although 16,000 Americans are on the liver transplant waiting list, only 6,000 liver transplants are performed each year in the United States. To overcome the scarcity of liver donors, the Program is investigating two distinct strategies to better treat liver disease, potentially through inducing regeneration. The first strategy is to generate patient-specific hepatocyte-like cells from directed differentiation of patient-induced pluripotent stem cell (iPSC) for liver cell therapy; and the second strategy is to promote activation of liver progenitor cells to produce de novo hepatocytes to replenish the damaged liver.
Liver regeneration via iPSC-derived cell therapy
Scientists from the Program are currently modeling the above listed genetic liver diseases in vitro by directed differentiation of induced pluripotent stem cell lines from patients into hepatocyte-like cells. The mutated liver gene is typically corrected through gene editing technologies, such as CRISPR/Cas9, in order to produce patient-specific edited hepatocyte-like cells for personalized liver cell therapy.
Various mouse models mimicking acute and chronic human liver diseases are currently established to test and validate the usefulness of human iPSC-derived hepatocyte-like cells to treat acute and chronic liver disease and the genetic liver diseases with edited cells.
Liver regeneration via activation of liver progenitor cells (LPC)
Although the liver has a robust ability to self-regenerate through the proliferation of mature hepatocytes, in the case of acute or chronic liver injury, proliferation of mature cells can be exhausted. Liver repair in most acute and chronic liver diseases in human is thus associated with expansion of LPCs in a process termed ductular reaction that is thought to contribute to liver regeneration. Scientists from the Program are currently testing tools to activate LPCs to promote innate liver repair.
To read more about this Program, please click on the links for each of our labs, all located on a single floor of our 16,000 square ft CReM stem cell facility
BU Amyloid Treatment and Research Program
The Alpha-1 Center of BU/BMC