Journal
AMERICAN JOURNAL OF TRANSPLANTATION
Volume 22, Issue 3, Pages 731-744Publisher
ELSEVIER SCIENCE INC
DOI: 10.1111/ajt.16928
Keywords
artificial organs; support devices; bioengineering; liver transplantation; hepatology; regenerative medicine; tissue; organ engineering; translational research; science
Categories
Funding
- Japan Agency for Medical Research and Development [17bm0404004h0005, 18bm0404038h0001]
- NIH Clinical Center [DK096990, DK099257, DK117881, DK119973, TR002383, TR003289]
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This study engineered a human-scale transplantable liver graft using a porcine liver-derived scaffold and evaluated its performance for 28 days using a preclinical large animal model. The results showed improvement in liver function after transplantation.
Unlimited organ availability would represent a paradigm shift in transplantation. Long-term in vivo engraftment and function of scaled-up bioengineered liver grafts have not been previously reported. In this study, we describe a human-scale transplantable liver graft engineered on a porcine liver-derived scaffold. We repopulated the scaffold parenchyma with primary hepatocytes and the vascular system with endothelial cells. For in vivo functional testing, we performed auxiliary transplantation of the repopulated scaffold in pigs with induced liver failure. It was observed that the auxiliary bioengineered liver graft improved liver function for 28 days and exhibited upregulation of liver-specific genes. This study is the first of its kind to present 28 days of posttransplant evaluation of a bioengineered liver graft using a preclinical large animal model. Furthermore, it provides definitive evidence for the feasibility of engineering human-scale transplantable liver grafts for clinical applications.
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