Human hepatic stem cells from fetal and postnatal donors

Schmelzer, Eva; Zhang, Lili; Bruce, Andrew; Wauthier, Eliane; Ludlow, John; Yao, Hsin-lei; Moss, Nicholas; Melhem, Alaa; McClelland, Randall; Turner, William; Kulik, Michael; Sherwood, Sonya; Tallheden, Tommi; Cheng, Nancy; Furth, Mark E.; Reid, Lola M.

doi:10.1084/jem.20061603

Title: Human hepatic stem cells from fetal and postnatal donors

Journal Article · Mon Jul 30 00:00:00 EDT 2007 · Journal of Experimental Medicine

DOI:https://doi.org/10.1084/jem.20061603· OSTI ID:1625191

Schmelzer, Eva ^[1]; Zhang, Lili ^[1]; Bruce, Andrew ^[2]; Wauthier, Eliane ^[1]; Ludlow, John ^[2]; Yao, Hsin-lei ^[3]; Moss, Nicholas ^[1]; Melhem, Alaa ^[1]; McClelland, Randall ^[1]; Turner, William ^[3]; Kulik, Michael ^[2]; Sherwood, Sonya ^[2]; Tallheden, Tommi ^[1]; Cheng, Nancy ^[1]; Furth, Mark E. ^[4]; Reid, Lola M. ^[5]

Univ. of North Carolina, Chapel Hill, NC (United States). Dept. of Cell and Molecular Physiology
Vesta Therapeutics, Durham, NC (United States)
Univ. of North Carolina, Chapel Hill, NC (United States). Depts. of Cell and Molecular Physiology and Biomedical Engineering
Wake Forest Baptist Medical Center, Winston Salem, NC (United States). Inst. for Regenerative Medicine
Univ. of North Carolina, Chapel Hill, NC (United States). Depts. of Cell and Molecular Physiology and Biomedical Engineering; Univ. of North Carolina, Chapel Hill, NC (United States). School of Medicine. Program in Molecular Biology and Biotechnology

Human hepatic stem cells (hHpSCs), which are pluripotent precursors of hepatoblasts and thence of hepatocytic and biliary epithelia, are located in ductal plates in fetal livers and in Canals of Hering in adult livers. They can be isolated by immunoselection for epithelial cell adhesion molecule–positive (EpCAM+) cells, and they constitute ~0.5–2.5% of liver parenchyma of all donor ages. The self-renewal capacity of hHpSCs is indicated by phenotypic stability after expansion for >150 population doublings in a serum-free, defined medium and with a doubling time of ~36 h. Survival and proliferation of hHpSCs require paracrine signaling by hepatic stellate cells and/or angioblasts that coisolate with them. The hHpSCs are ~9 μm in diameter, express cytokeratins 8, 18, and 19, CD133/1, telomerase, CD44H, claudin 3, and albumin (weakly). They are negative for α-fetoprotein (AFP), intercellular adhesion molecule (ICAM) 1, and for markers of adult liver cells (cytochrome P450s), hemopoietic cells (CD45), and mesenchymal cells (vascular endothelial growth factor receptor and desmin). If transferred to STO feeders, hHpSCs give rise to hepatoblasts, which are recognizable by cordlike colony morphology and up-regulation of AFP, P4503A7, and ICAM1. Transplantation of freshly isolated EpCAM+ cells or of hHpSCs expanded in culture into NOD/SCID mice results in mature liver tissue expressing human-specific proteins. The hHpSCs are candidates for liver cell therapies.

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Research Organization:: University of North Carolina, Chapel Hill, NC (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: FG02-02ER-63477; RO1 DK52851; RO1 AA014243; RO1 IP30-DK065933

OSTI ID:: 1625191

Journal Information:: Journal of Experimental Medicine, Vol. 204, Issue 8; ISSN 0022-1007

Publisher:: Rockefeller University PressCopyright Statement

Country of Publication:: United States

Language:: English

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Monoclonal Antibodies 13A4 and AC133 Do Not Recognize the Canine Ortholog of Mouse and Human Stem Cell Antigen Prominin-1 (CD133) Thamm, Kristina; Graupner, Sylvi; Werner, Carsten PLOS ONE, Vol. 11, Issue 10 https://doi.org/10.1371/journal.pone.0164079	journal	October 2016
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Hepatic progenitors for liver disease: current position Kisseleva, Tatiana Stem Cells and Cloning: Advances and Applications https://doi.org/10.2147/sccaa.s6035	journal	February 2010
Progress in stem cell-derived technologies for hepatocellular carcinoma Aravalli, Raj Stem Cells and Cloning: Advances and Applications https://doi.org/10.2147/sccaa.s6886	journal	May 2010
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A Transcriptomic Signature of Mouse Liver Progenitor Cells Passman, Am; Low, J.; London, R. La Trobe https://doi.org/10.26181/19729978	text	January 2022
The Use of Cellular Technologies in Treatment of Liver Pathologies Petrakova, O. S.; Chernioglo, E. S.; Terskikh, V. V. Acta Naturae, Vol. 4, Issue 3 https://doi.org/10.32607/20758251-2012-4-3-16-30	journal	September 2012
Functions and the Emerging Role of the Foetal Liver into Regenerative Medicine Cells, Vol. 8, Issue 8 https://doi.org/10.3390/cells8080914	journal	August 2019
Potential and Challenges of Induced Pluripotent Stem Cells in Liver Diseases Treatment Yu, Yue; Wang, Xuehao; Nyberg, Scott Journal of Clinical Medicine, Vol. 3, Issue 3 https://doi.org/10.3390/jcm3030997	journal	September 2014
Road to stemness in hepatocellular carcinoma Flores-Téllez, Teresita NJ; Villa-Treviño, Saúl; Piña-Vázquez, Carolina World Journal of Gastroenterology, Vol. 23, Issue 37 https://doi.org/10.3748/wjg.v23.i37.6750	journal	October 2017
Yiguanjian decoction enhances fetal liver stem/progenitor cell-mediated repair of liver cirrhosis through regulation of macrophage activation state Xu, Ying; Fan, Wei-Wei; Xu, Wen World Journal of Gastroenterology, Vol. 24, Issue 42 https://doi.org/10.3748/wjg.v24.i42.4759	journal	November 2018
Circular RNA profile in liver tissue of EpCAM knockout mice Yang, Yanhong; Liu, Shaomin; Lei, Zili International Journal of Molecular Medicine https://doi.org/10.3892/ijmm.2019.4270	journal	July 2019
CD133 expression and α‑fetoprotein levels define novel prognostic subtypes of HBV‑associated hepatocellular carcinoma: A long‑term follow‑up analysis Dai, Xiao‑Meng; Yang, Sheng‑Li; Zheng, Xiu‑Mei Oncology Letters https://doi.org/10.3892/ol.2017.7704	journal	December 2017
Tissue-Derived Stem and Progenitor Cells Tesche, Leora J.; Gerber, David A. Stem Cells International, Vol. 2010 https://doi.org/10.4061/2010/824876	journal	January 2010
The Emerging Role of MicroRNAs in Hepatocellular Carcinoma Akkiz, Hikmet Euroasian Journal of Hepato-Gastroenterology, Vol. 4, Issue 1 https://doi.org/10.5005/jp-journals-10018-1095	journal	January 2013
Reprogramming Somatic Cells by Fusion with Embryonic Stem Cells: Present Status and Prospects in Regenerative Medicine Han, Jinnuo; Sidhu, Kuldip S. Methodological Advances in the Culture, Manipulation and Utilization of Embryonic Stem Cells for Basic and Practical Applications https://doi.org/10.5772/14323	book	April 2011
Liver Regeneration: the Role of Bioengineering Baptista, Pedro M.; Vyas, Dipen; Soker, Shay Progress in Molecular and Environmental Bioengineering - From Analysis and Modeling to Technology Applications https://doi.org/10.5772/21549	book	August 2011
Hepatocytes and Progenitor - Stem Cells in Regeneration and Therapy Amicone, Laura; Citarella, Franca; Tripodi, Marco Liver Regeneration https://doi.org/10.5772/45602	book	May 2012
Liver Regeneration and Bioengineering - The Emergence of Whole Organ Scaffolds Baptista, Pedro M.; Vyas, Dipen; Soker, Shay Liver Regeneration https://doi.org/10.5772/45984	book	May 2012
Liver Progenitor Cells, Cancer Stem Cells and Hepatocellular Carcinoma Tirnitz-Parker, Janina E. E.; Yeoh, George C. T.; Olynyk, John K. Liver Regeneration https://doi.org/10.5772/48005	book	May 2012
Adult Hepatic Progenitor Cells Vestentoft, Peter Siig Adult Stem Cell Niches https://doi.org/10.5772/58814	book	August 2014
Cancer Stem Cells and Aldehyde Dehydrogenase 1 in Liver Cancers Tomita, Hiroyuki; Kanayama, Tomohiro; Niwa, Ayumi Updates in Liver Cancer https://doi.org/10.5772/66454	book	April 2017
Regenerative Medicine in Liver Cirrhosis: Promises and Pitfalls Tayyeb, Asima; Azam, Fareeha; Nisar, Rabia Liver Cirrhosis - Update and Current Challenges https://doi.org/10.5772/intechopen.68729	book	July 2017
Novel therapeutic Strategies for Targeting Liver Cancer Stem Cells Oishi, Naoki; Wang, Xin Wei International Journal of Biological Sciences, Vol. 7, Issue 5 https://doi.org/10.7150/ijbs.7.517	journal	January 2011

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Title: Human hepatic stem cells from fetal and postnatal donors

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