Coexpression of platelet-derived growth factor receptor alpha and fetal liver kinase 1 enhances cardiogenic potential in embryonic stem cell differentiation in vitro
2007
Hirata, H.(Foundation of Biomedical Research and Innovation, Kobe (Japan)) | Kawamata, S. | Murakami, Y. | Inoue, K. | Nagahashi, A. | Tosaka, M. | Yoshimura, N. | Miyamoto, Y. | Iwasaki, H. | Asahara, T. | Sawa, Y.
Nascent mesodermal cells derived from EB5 embryonic stem (ES) cells were sorted in terms of cardiogenic potential on the basis of their expression levels of platelet-derived growth factor receptor alpha (PDGFRalpha) and fetal liver kinase 1 (Flk-1). The sorted cells were cocultured with OP9 stromal cells to induce terminal differentiation into contractile cardiac colonies. A significant number of cardiac colonies were found in the Flk-1+/PDGFRalpha+ fraction. The enrichment double-positive fraction produced approximately fivefold more cardiac colonies than the Flk-1+/PDGFRalpha- fraction and 10-fold more than the Flk-1-/PDGFRalpha+ fraction. To investigate the involvement of these markers in embryonic cardiogenesis, the cells that disseminated from the E7.5-7.75 embryos were fractionated and seeded on OP9 cells. The cardiogenic potential was markedly enhanced in the Flk-1+/PDGFRalpha+ fraction. These results suggest that some of the precursor cells coexpressing these markers are selectively involved in cardiogenic events, and that the identification of ES-cell-derived precursors with these markers will contribute to the effective production of cardiomyocytes for cell therapies.
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