Original Article
Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Oct 21, 2009; 15(39): 4896-4906
Published online Oct 21, 2009. doi: 10.3748/wjg.15.4896
Characterization of CD133+ parenchymal cells in the liver: Histology and culture
Seiichi Yoshikawa, Yoh Zen, Takahiko Fujii, Yasunori Sato, Tetsuo Ohta, Yutaka Aoyagi, Yasuni Nakanuma
Seiichi Yoshikawa, Takahiko Fujii, Yasunori Sato, Yasuni Nakanuma, Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan
Seiichi Yoshikawa, Yutaka Aoyagi, Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
Yoh Zen, Division of Pathology, Kanazawa University Hospital, Kanazawa 920-8641, Japan
Tetsuo Ohta, Department of Gastrointestinal Surgery, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan
Author contributions: Yoshikawa S performed the majority of experiments and wrote the manuscript; Zen Y, Fujii T and Sato Y performed the technical aspects of the experiments; Ohta T collected the human materials; Aoyagi Y and Nakanuma Y provided financial support for this work and designed the study.
Correspondence to: Dr. Yasuni Nakanuma, MD, Department of Human Pathology, Kanazawa University Graduate School of Medicine, 13-1 Takaramachi, Kanazawa 920-8640, Japan. pbcpsc@kenroku.kanazawa-u.ac.jp
Telephone: +81-76-2652195 Fax: +81-76-2344229
Received: June 11, 2009
Revised: August 4, 2009
Accepted: August 11, 2009
Published online: October 21, 2009

AIM: To reveal the characteristics of CD133+ cells in the liver.

METHODS: This study examined the histological characteristics of CD133+ cells in non-neoplastic and neoplastic liver tissues by immunostaining, and also analyzed the biological characteristics of CD133+ cells derived from human hepatocellular carcinoma (HCC) or cholangiocarcinoma cell lines.

RESULTS: Immunostaining revealed constant expression of CD133 in non-neoplastic and neoplastic biliary epithelium, and these cells had the immunophenotype CD133+/CK19+/HepPar-1-. A small number of CD133+/CK19-/HepPar-1+ cells were also identified in HCC and combined hepatocellular and cholangiocarcinoma. In addition, small ductal structures, resembling the canal of Hering, partly surrounded by hepatocytes were positive for CD133. CD133 expression was observed in three HCC (HuH7, PLC5 and HepG2) and two cholangiocarcinoma cell lines (HuCCT1 and CCKS1). Fluorescence-activated cell sorting (FACS) revealed that CD133+ and CD133- cells derived from HuH7 and HuCCT1 cells similarly produced CD133+ and CD133- cells during subculture. To examine the relationship between CD133+ cells and the side population (SP) phenotype, FACS was performed using Hoechst 33342 and a monoclonal antibody against CD133. The ratios of CD133+/CD133- cells were almost identical in the SP and non-SP in HuH7. In addition, four different cellular populations (SP/CD133+, SP/CD133-, non-SP/CD133+, and non-SP/CD133-) could similarly produce CD133+ and CD133- cells during subculture.

CONCLUSION: This study revealed that CD133 could be a biliary and progenitor cell marker in vivo. However, CD133 alone is not sufficient to detect tumor-initiating cells in cell lines.

Keywords: Cholangiocarcinoma, Hepatocellular carcinoma, Keratins, Stem cells