Hepatocyte-like cells generated by direct reprogramming from murine somatic cells can repopulate decellularized livers

TY - JOUR

T1 - Hepatocyte-like cells generated by direct reprogramming from murine somatic cells can repopulate decellularized livers

AU - Chen, Chen

AU - Pla-Palacín, Iris

AU - Baptista, Pedro M

AU - Shang, Peng

AU - Oosterhoff, Loes A

AU - van Wolferen, Monique E

AU - Penning, Louis C

AU - Geijsen, Niels

AU - Spee, Bart

N1 - © 2018 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.

PY - 2018/11

Y1 - 2018/11

N2 - 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.

AB - 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.

U2 - 10.1002/bit.26784

DO - 10.1002/bit.26784

M3 - Article

C2 - 29959867

SN - 0006-3592

VL - 115

SP - 2807

EP - 2816

JO - Biotechnology and Bioengineering

JF - Biotechnology and Bioengineering

IS - 11

ER -