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American Liver Foundation
39 Broadway, Suite 2700
New York, New York 10006
American Association for the Study of Liver Diseases/American Liver Foundation Liver Scholar Award
Project Title: Liver Tissue Engineering: Novel methods for Organ Design and Animal Model Development
Dr. Wertheim’s research proposes to develop a rodent model of liver tissue engineering. The future clinical application of this research is the development of “Just-in-time organs”, reconstituted with recipient derived cells, which will abrogate the need for long waitlist times and associated waitlist mortality, reduce the reliance on organs from living donors, and potentially obviate the need for immunosuppression. Conceptually, this process will remove the antigenic parenchyma from either non-transplantable human organs (e.g. livers with steatosis) or pig organs, leaving only the extracellular matrix (ECM) as a scaffold. Once a patient with early liver failure has been identified, a skin biopsy or blood sample can be used to derive hepatocytes and endothelial cells from the intended recipient using induced pluripotent stem (iPS) cell technology. The organ ECM may then be repopulated with these mature cells derived from the intended recipient. After weeks to months of growth in a bioreactor leading to organ maturation, the tissue engineered liver would be ready to implant into the recipient “on demand”. To develop an animal model of this approach, the goals of Dr. Wertheim’s proposal are directed at developing optimal protocols for removing the cellular components of donor rat livers, combining the resulting matrix with endothelial cells and hepatocytes derived using iPS technology and evaluation of organ function upon implantation into a rodent recipient. Together, this work represents novel advances in regenerative medicine to develop an animal model of liver tissue engineering with future implications as a clinical treatment for acute and chronic liver failure.
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