Effect of Donor Age and Liver Steatosis on Potential of Decellularized Liver Matrices to Be Used as A Platform for Ipsc‐Hepatocyte Culture

Abstract

AbstractDecellularization of discarded whole livers and their recellularization with patient‐specific induced pluripotent stem cells (iPSCs) to develop a functional organ is a promising approach to increase donor pool. The effect of extracellular matrix (ECM) of marginal livers on iPSC‐hepatocyte differentiation and function has not been shown. To test the effect of donor liver ECM age and steatosis, we decellularized young, old, as well as no, low and high steatosis livers. All livers were decellularized successfully. High steatosis livers had fat remaining on the ECM after decellularization. Old donor liver ECM induced lower marker expression in early differentiation stages, compared to young liver ECM, while this difference was closed at later stages and did not affect iPSC‐hepatocyte function significantly. High steatosis levels of liver ECM led to higher albumin mRNA expression and secretion while at later stages of differentiation expression of major CYP450 enzymes was highest in low steatosis liver ECM. Both primary human hepatocytes and iPSC‐hepatocytes showed an increase in fat metabolism marker expression with increasing steatosis levels most likely induced by excess fat remaining on the ECM. Overall, removal of excess fat from liver ECM may be needed for inducing proper hepatic function after recellularization.This article is protected by copyright. All rights reserved