Murine "cardiospheres" are not a source of stem cells with cardiomyogenic potential

Ditte Caroline Andersen, Peter Andersen, Mikael Schneider, Hasse Brønnum Jensen, Søren Paludan Sheikh

Research output: Contribution to journalArticle

Abstract

Recent remarkable studies have reported that clonogenic putative cardiac stem cells (CSCs) with cardiomyogenic potential migrate from heart tissue biopsies during ex vivo culture, and that these CSCs self-organize into spontaneously beating cardiospheres (CSs). Such data have provided clear promise that injured heart tissue may be repaired by stem cell therapy using autologous CS-derived cells. By further examining CSs from the original CS protocol using immunofluorescence, quantitative reverse transcription-polymerase chain reaction, and microscopic analysis, we here report a more mundane result: that spontaneously beating CSs from neonatal rats likely consist of contaminating myocardial tissue fragments. Thus, filtering away these tissue fragments resulted in CSs without cardiomyogenic potential. Similar data were obtained with CSs derived from neonatal mice as wells as adult rats/mice. Additionally, using in vitro culture, fluorescence-activated cell sorting, and immunofluorescence, we demonstrate that these CSs are generated by cellular aggregation of GATA-4+/collagen I+/α-smooth muscle actin (SMA)+/CD45- cells rather than by clonal cell growth. In contrast, we found that the previously proposed CS-forming cells, dubbed phase bright cells, were GATA-4-/collagen I -/α-SMA-/CD45+ and unable to form CSs by themselves. Phenotypically, the CS cells largely resembled fibroblasts, and they lacked cardiomyogenic as well as endothelial differentiation potential. Our data imply that the murine CS model is unsuitable as a source of CSCs with cardiomyogenic potential, a result that is in contrast to previously published data. We therefore suggest, that human CSs should be further characterized with respect to phenotype and differentiation potential before initiating human trials.

Original languageEnglish (US)
Pages (from-to)1571-1581
Number of pages11
JournalStem Cells
Volume27
Issue number7
DOIs
StatePublished - Jul 2009
Externally publishedYes

Fingerprint

Stem Cells
Fluorescent Antibody Technique
Smooth Muscle
Actins
Collagen
Cell- and Tissue-Based Therapy
Reverse Transcription
Flow Cytometry
Fibroblasts
Phenotype
Biopsy
Polymerase Chain Reaction
Growth

Keywords

  • Adult stem cells
  • Cardiac
  • Cell culture
  • Differentiation
  • Myofibroblast
  • Myogenesis

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

Andersen, D. C., Andersen, P., Schneider, M., Jensen, H. B., & Sheikh, S. P. (2009). Murine "cardiospheres" are not a source of stem cells with cardiomyogenic potential. Stem Cells, 27(7), 1571-1581. https://doi.org/10.1002/stem.72

Murine "cardiospheres" are not a source of stem cells with cardiomyogenic potential. / Andersen, Ditte Caroline; Andersen, Peter; Schneider, Mikael; Jensen, Hasse Brønnum; Sheikh, Søren Paludan.

In: Stem Cells, Vol. 27, No. 7, 07.2009, p. 1571-1581.

Research output: Contribution to journalArticle

Andersen, DC, Andersen, P, Schneider, M, Jensen, HB & Sheikh, SP 2009, 'Murine "cardiospheres" are not a source of stem cells with cardiomyogenic potential', Stem Cells, vol. 27, no. 7, pp. 1571-1581. https://doi.org/10.1002/stem.72
Andersen, Ditte Caroline ; Andersen, Peter ; Schneider, Mikael ; Jensen, Hasse Brønnum ; Sheikh, Søren Paludan. / Murine "cardiospheres" are not a source of stem cells with cardiomyogenic potential. In: Stem Cells. 2009 ; Vol. 27, No. 7. pp. 1571-1581.
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