Immunohistochemical and flow cytometric analysis of long-term label-retaining cells in the adult heart.

Details

Serval ID
serval:BIB_8DB8C58C983B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Immunohistochemical and flow cytometric analysis of long-term label-retaining cells in the adult heart.
Journal
Stem Cells and Development
Author(s)
Meinhardt A., Spicher A., Roehrich M.E., Glauche I., Vogt P., Vassalli G.
ISSN
1557-8534[electronic], 1547-3287[linking]
Publication state
Published
Issued date
2011
Volume
20
Number
2
Pages
211-222
Language
english
Abstract
Cardiac-resident stem/progenitor cells have been identified based on expression of stem cell-associated antigens. However, no single surface marker allows to identify a definite cardiac stem/progenitor cell entity. Hence, functional stem cell markers have been extensively searched for. In homeostatic systems, stem cells divide infrequently and therefore retain DNA labels such as 5-bromo-2'-deoxyuridine, which are diluted with division. We used this method to analyze long-term label-retaining cells in the mouse heart after 14 days of 5-bromo-2'-deoxyuridine administration. Labeled cells were detected using immunohistochemical and flow-cytometric methods after varying chasing periods up to 12 months. Using mathematical models, the observed label dilution could consistently be described in the context of a 2-population model, whereby a population of rapidly dividing cells accounted for an accelerated early decline, and a population of slowly dividing cells accounted for decelerated dilution on longer time scales. Label-retaining cells were preferentially localized in the atria and apical region and stained negative for markers of the major cell lineages present in the heart. Most cells with long-term label-retention expressed stem cell antigen-1 (Sca-1). Sca-1(+)CD31(-) cells formed cell aggregates in culture, out of which lineage-negative (Lin(-))Sca-1(+)CD31(-) cells emerged, which could be cultured for many passages. These cells formed cardiospheres and showed differentiation potential into mesenchymal cell lineages. When cultured in cardiomyogenic differentiation medium, they expressed cardiac-specific genes. In conclusion, recognition of slow-cycling cells provides functional evidence of stem/progenitor cells in the heart. Lin(-)Sca-1(+)CD31(-) cardiac-derived progenitors have a potential for differentiation into cardiomyogenic and mesenchymal cell lineages.
Pubmed
Web of science
Create date
23/02/2011 8:49
Last modification date
20/08/2019 14:51
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