Open AccessAnalysis of the Origin and Population Dynamics of Cardiac Progenitor Cells in a Donor Heart Model
Author(s) -
Li TaoSheng,
Suzuki Ryo,
Ueda Kazuhiro,
Murata Tomoaki,
Hamano Kimikazu
Publication year - 2007
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2006-0497
Subject(s) - biology , immunostaining , progenitor cell , stem cell , cd34 , population , transplantation , side population , haematopoiesis , green fluorescent protein , flow cytometry , immunology , microbiology and biotechnology , bone marrow , andrology , medicine , immunohistochemistry , cancer stem cell , gene , genetics , environmental health
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.