Sambathkumar, Rangarajan, Akkerman, Renate, Dastidar, Sumitava, Roelandt, Philip, Kumar, Manoj, Bajaj, Manmohan, Mestre Rosa, Ana Rita, Helsen, Nicky, Vanslembrouck, Veerle, Kalo, Eric, Khurana, Satish, Laureys, Jos, Gysemans, Conny, Faas, Marijke M., de Vos, Paul, and Verfaillie, Catherine M. (2018) Generation of hepatocyte- and endocrine pancreatic-like cells from human induced endodermal progenitor cells. PLoS ONE, 13 (5). e0197046.

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Abstract

Multipotent Adult Progenitor Cells (MAPCs) are one potential stem cell source to generate functional hepatocytes or β-cells. However, human MAPCs have less plasticity than pluripotent stem cells (PSCs), as their ability to generate endodermal cells is not robust. Here we studied the role of 14 transcription factors (TFs) in reprogramming MAPCs to induced endodermal progenitor cells (iENDO cells), defined as cells that can be long-term expanded and differentiated to both hepatocyte- and endocrine pancreatic-like cells. We demonstrated that 14 TF-iENDO cells can be expanded for at least 20 passages, differentiate spontaneously to hepatocyte-, endocrine pancreatic-, gut tube-like cells as well as endodermal tumor formation when grafted in immunodeficient mice. Furthermore, iENDO cells can be differentiated in vitro into hepatocyte- and endocrine pancreatic-like cells. However, the pluripotency TF OCT4, which is not silenced in iENDO cells, may contribute to the incomplete differentiation to mature cells in vitro and to endodermal tumor formation in vivo. Nevertheless, the studies presented here provide evidence that reprogramming of adult stem cells to an endodermal intermediate progenitor, which can be expanded and differentiate to multiple endodermal cell types, might be a valid alternative for the use of PSCs for creation of endodermal cell types.

Item ID:	86143
Item Type:	Article (Research - C1)
ISSN:	1932-6203
Related URLs:	https://journals.plos.org/plosone/articl...
Copyright Information:	© 2018 Sambathkumar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Date Deposited:	16 Jul 2025 23:02
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3206 Medical biotechnology > 320606 Regenerative medicine (incl. stem cells) @ 70% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320208 Endocrinology @ 20% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3206 Medical biotechnology > 320699 Medical biotechnology not elsewhere classified @ 10%
SEO Codes:	20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions @ 100%
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