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Mol. Cells 2013; 36(5): 424-431

Published online November 30, 2013

https://doi.org/10.1007/s10059-013-0190-y

© The Korean Society for Molecular and Cellular Biology

Isolation of EpCAM+/CD133? Hepatic Progenitor Cells

Pei-Pei Hao, Mi-Jin Lee, Goung-Ran Yu, In-Hee Kim, Yong-Gon Cho, and Dae-Ghon Kim

Division of Gastroenterology and Hepatology, Departments of Internal Medicine, 1Laboratory Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital, Jeonju 561-712, Korea

Received: July 1, 2013; Revised: September 12, 2013; Accepted: September 17, 2013

Abstract

Progenitor cell-derived hepatocytes are critical for hepatocyte replenishment. Therefore, we established a line of human hepatic progenitor (HNK1) cells and determined their biological characteristics for experimental and therapeutic applications. HNK1 cells, isolated from human noncirrhotic liver samples with septal fibrosis, showed high expression of the hepatic progenitor cell (HPC) markers EpCAM, CK7, CK19, alpha-fetoprotein (AFP), CD90 (Thy1), and EFNA1. Expression of CD133 was very low. Ductular reactions at the periphery of cirrhotic nodules were immunohistochemically positive for these HPC markers, including EFNA1. Sodium butyrate, a differentiation inducer, in-duced hepatocyte-like morphological changes in HNK1 cells. It resulted in down-regulation of the hepatic progenitor cell markers EpCAM, CK7, CK19, AFP, and EFNA1 and up-regulation of mature hepatocyte markers, including albumin, CK8, and CK18. Furthermore, sodium butyrate treatment and a serial passage of HNK1 cells resulted in enhanced albumin secretion, ureagenesis, and CYP enzyme activity, all of which are indicators of differentiation in hepatocytes. However, HNK1 cells at passage 50 did not exhibit anchorage-independent growth capability and caused no tumors in immunodeficient mice, suggesting that they had no spontaneous malignant transformation ability. From this evidence, HNK1 cells were found to be EpCAM+/ CD133? hepatic progenitor cells without spontaneous malignant transformation ability. We therefore conclude that HNK1 cells could be useful for experimental and therapeutic applications.

Keywords CD133, EFNA1, EpCAM, hepatic progenitor cells, malignant transformation

Article

Research Article

Mol. Cells 2013; 36(5): 424-431

Published online November 30, 2013 https://doi.org/10.1007/s10059-013-0190-y

Copyright © The Korean Society for Molecular and Cellular Biology.

Isolation of EpCAM+/CD133? Hepatic Progenitor Cells

Pei-Pei Hao, Mi-Jin Lee, Goung-Ran Yu, In-Hee Kim, Yong-Gon Cho, and Dae-Ghon Kim

Division of Gastroenterology and Hepatology, Departments of Internal Medicine, 1Laboratory Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital, Jeonju 561-712, Korea

Received: July 1, 2013; Revised: September 12, 2013; Accepted: September 17, 2013

Abstract

Progenitor cell-derived hepatocytes are critical for hepatocyte replenishment. Therefore, we established a line of human hepatic progenitor (HNK1) cells and determined their biological characteristics for experimental and therapeutic applications. HNK1 cells, isolated from human noncirrhotic liver samples with septal fibrosis, showed high expression of the hepatic progenitor cell (HPC) markers EpCAM, CK7, CK19, alpha-fetoprotein (AFP), CD90 (Thy1), and EFNA1. Expression of CD133 was very low. Ductular reactions at the periphery of cirrhotic nodules were immunohistochemically positive for these HPC markers, including EFNA1. Sodium butyrate, a differentiation inducer, in-duced hepatocyte-like morphological changes in HNK1 cells. It resulted in down-regulation of the hepatic progenitor cell markers EpCAM, CK7, CK19, AFP, and EFNA1 and up-regulation of mature hepatocyte markers, including albumin, CK8, and CK18. Furthermore, sodium butyrate treatment and a serial passage of HNK1 cells resulted in enhanced albumin secretion, ureagenesis, and CYP enzyme activity, all of which are indicators of differentiation in hepatocytes. However, HNK1 cells at passage 50 did not exhibit anchorage-independent growth capability and caused no tumors in immunodeficient mice, suggesting that they had no spontaneous malignant transformation ability. From this evidence, HNK1 cells were found to be EpCAM+/ CD133? hepatic progenitor cells without spontaneous malignant transformation ability. We therefore conclude that HNK1 cells could be useful for experimental and therapeutic applications.

Keywords: CD133, EFNA1, EpCAM, hepatic progenitor cells, malignant transformation

Mol. Cells
Nov 30, 2022 Vol.45 No.11, pp. 763~867
COVER PICTURE
Naive (cyan) and axotomized (magenta) retinal ganglion cell axons in Xenopus tropicalis (Choi et al., pp. 846-854).

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