HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 2007-0199v1 2007-0199v2 25/12/3252    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ishii, T. Articles by Ikai, I. Search for Related Content PubMed PubMed Citation Articles by Ishii, T. Articles by Ikai, I.

TRANSLATIONAL AND CLINICAL RESEARCH

Transplantation of Embryonic Stem Cell-Derived Endodermal Cells into Mice with Induced Lethal Liver Damage

^aDepartment of Surgery, Graduate School of Medicine,
^bLaboratory of Embryonic Stem Cell Research, Stem Cell Research Center, and
^cDepartment of Development and Differentiation, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan;
^dGraduate School of Biological Sciences, Nara Institute of Science and Technology, Nara, Japan

Key Words. Embryonic stem cell • Cell transplantation • -Fetoprotein • Hepatocyte differentiation

Correspondence: Iwao Ikai, M.D., Ph.D., 54 Kawahara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. Telephone: 81-75-751-3242; Fax: 81-75-751-4263; e-mail: ikai{at}kuhp.kyoto-u.ac.jp

Received March 22, 2007; accepted for publication September 11, 2007.
First published online in STEM CELLS EXPRESS   September 20, 2007.



ESCs are a potential cell source for cell therapy. However, there is no evidence that cell transplantation using ESC-derived hepatocytes is therapeutically effective. The main objective of this study was to assess the therapeutic efficacy of the transplantation of ESC-derived endodermal cells into a liver injury model. The β-galactosidase-labeled mouse ESCs were differentiated into -fetoprotein (AFP)-producing endodermal cells. AFP-producing cells or ESCs were transplanted into transgenic mice that expressed diphtheria toxin (DT) receptors under the control of an albumin enhancer/promoter. Selective damage was induced in the recipient hepatocytes by the administration of DT. Although the transplanted AFP-producing cells had repopulated only 3.4% of the total liver mass 7 days after cell transplantation, they replaced 32.8% of the liver by day 35. However, these engrafted cells decreased (18.3% at day 40 and 7.9% at day 50) after the cessation of DT administration, and few donor cells were observed by days 60–90. The survival rate of the AFP-producing cell-transplanted group (66.7%) was significantly higher in comparison with that of the sham-operated group (17.6%). No tumors were detected by day 50 in the AFP-producing cell-transplanted group; however, splenic teratomas did form 60 days or more after transplantation. ESC transplantation had no effect on survival rates; furthermore, there was a high frequency of tumors in the ESC-transplanted group 35 days after transplantation. In conclusion, this study demonstrates, for the first time, that ESC-derived endodermal cells improve the survival rates after transplantation into mice with induced hepatocellular injury.

Disclosure of potential conflicts of interest is found at the end of this article.