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Hepatocyte‐like cells generated by direct reprogramming from murine somatic cells can repopulate decellularized livers
Author(s) -
Chen Chen,
PlaPalacín Iris,
Baptista Pedro M.,
Shang Peng,
Oosterhoff Loes A.,
Wolferen Monique E.,
Penning Louis C.,
Geijsen Niels,
Spee Bart
Publication year - 2018
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.26784
Subject(s) - reprogramming , hepatocyte , decellularization , somatic cell , microbiology and biotechnology , embryonic stem cell , biology , cell , liver cytology , chemistry , in vitro , biochemistry , gene , liver metabolism , extracellular matrix
Direct reprogramming represents an easy technique to generate induced hepatocytes (iHeps) from somatic cells. However, current protocols are accompanied by several drawbacks as iHeps are heterogenous and lack fully mature phenotypes of primary hepatocytes. Here, we established a polycistronic expression system to induce the direct reprogramming of mouse embryonic fibroblasts towards hepatocytes. The resulting iHeps are homogenous and display key properties of primary hepatocytes, such as expression of hepatocyte markers, albumin secretion, and presence of liver transaminases. iHeps also possess the capacity to repopulate decellularized liver tissue and exhibit enhanced hepatic maturation. As such, we present a novel strategy to generate homogenous and functional iHeps for applications in tissue engineering and cell therapy.