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: 2006-0497v1 25/4/911    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 Li, T.-S. Articles by Hamano, K. Search for Related Content PubMed PubMed Citation Articles by Li, T.-S. Articles by Hamano, K.

TISSUE-SPECIFIC STEM CELLS

Analysis of the Origin and Population Dynamics of Cardiac Progenitor Cells in a Donor Heart Model

Department of Surgery and Clinical Science and Institute of Laboratory Animals, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan

Key Words. Heart • Stem cell • Bone marrow

Correspondence: Tao-Sheng Li, M.D., Ph.D., Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan. Telephone: +81-836-222261; Fax: +81-836-222423; e-mail: litaoshe{at}yamaguchi-u.ac.jp

Received August 8, 2006; accepted for publication December 31, 2006.
First published online in STEM CELLS EXPRESS   January 11, 2007.



Cardiac progenitor (stem) cells have recently been detected in and isolated from the myocardium of neonatal and adult mice, rats, and humans; however, the precise origin and characterization of these cells remain unclear. Using a heterotopic mouse heart transplantation model, we investigated the origin and population dynamics of cardiac progenitor cells. Donor hearts from wild-type C57/BL6 female mice were transplanted into green fluorescent protein (GFP)-transgenic C57/BL6 male mice. The donor hearts were collected 0, 2, 4, 8, and 12 weeks after transplantation. We used quantitative flow cytometry to analyze the number and origin of stem cells in the donor hearts and immunostaining to evaluate the time-related changes in their characteristics. Extracardiac GFP-positive stem cells immigrated into the donor hearts soon after transplantation. Immunostaining revealed that these GFP-positive stem cells in the donor hearts gradually lost expression of the hematopoietic markers of CD45 and CD34 and shifted to express the cardiac-specific transcription factors GATA-4 and NKx2.5. A few of the GFP-positive cells in the donor hearts finally acquired the mature cardiac phenotype in the absence of cell fusion with donor cardiomyocytes. Our discovery provides the first evidence that extracardiac stem cells may be of bone marrow origin, from which they can transform into cardiac progenitor cells in response to myocardial environment cues.

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