The effect of decellularized liver matrix on stem cell differentiation into hepatocyte-like cells

Date
2016
Authors
Coronado, Ramon E.
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract

Liver transplantation is a commonly accepted life saving surgical, the major challenge facing the transplant community is a consequence of their great success; more organs for transplantation are now needed. The severe discrepancy between livers available for donation and the candidates' waiting list is a problem. Hepatocyte transplantation has been demonstrated to have a positive therapeutic effect. However, the application of this technology has been hindered by the inability to secure a reliable and healthy cell source(s), shortage of organ donors, problems related to isolation of high quality hepatocytes. Furthermore, hepatocytes do not proliferate and de-differentiate in vitro. Faced with that problem, stem cells (MSCs) had been considered as a candidate to substitute hepatocytes transplants. However, despite published results showing hepatocyte-like cells derived from different mesenchymal stem cells, only a limited group of unique molecules/functions are shown to be up-regulated. In order to improve the differentiation of hepatocyte-like cells, we developed a substrate made of solubilized decellularized porcine liver tissue and differentiated stem cells from various sources (adipose, bone marrow, amnion) into hepatocyte-like cells. We effectively decellularized liver tissue and successfully optimized the solubilization of the decellularized liver matrix (pLEACM-AA) to be used as a substrate for in vitro studies. The substrate had low immunogenicity and no cytotoxicity. A series of hepatocyte sequential differentiation protocols were evaluated on ASC, then we selected the protocol that yielded the best hepatocyte-like cell based on relevant functions (urea, P450 metabolism, LDL-uptake, glycogen storage, gene expression. Finally, we demonstrated that the liver tissue substrate (pLECM-AA) enhances the hepatocyte differentiation by doing RNAseq analysis of human ASC, BMMSC and AEC differentiated into hepatocyte cells while cultured on the pLECM-AA. These results highlight the importance of the native extracellular bioactivity and their impact on stem cell differentiation.

Description
This item is available only to currently enrolled UTSA students, faculty or staff. To download, navigate to Log In in the top right-hand corner of this screen, then select Log in with my UTSA ID.
Keywords
bone marrow, Decellularized, ECM, Hepatocyte, Liver, Stem Cell
Citation
Department
Biomedical Engineering