Sox2 Transduction enhances cardiovascular repair capacity of blood-derived mesoangioblasts

Masamichi Koyanagi, Masayoshi Iwasaki, Stefan Rupp, Francesco Saverio Tedesco, Chang Hwan Yoon, Jes Niels Boeckel, Janina Trauth, Corina Schütz, Kisho Ohtani, Rebekka Goetz, Kazuma Iekushi, Philipp Bushoven, Stefan Momma, Christine Mummery, Robert Passier, Reinhard Henschler, Hakan Akintuerk, Dietmar Schranz, Carmen Urbich, Beatriz G. GalvezGiulio Cossu, Andreas M. Zeiher, Stefanie Dimmeler

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28 Citations (Scopus)

Abstract

RATIONALE: Complementation of pluripotency genes may improve adult stem cell functions. OBJECTIVES: Here we show that clonally expandable, telomerase expressing progenitor cells can be isolated from peripheral blood of children. The surface marker profile of the clonally expanded cells is distinct from hematopoietic or mesenchymal stromal cells, and resembles that of embryonic multipotent mesoangioblasts. Cell numbers and proliferative capacity correlated with donor age. Isolated circulating mesoangioblasts (cMABs) express the pluripotency markers Klf4, c-Myc, as well as low levels of Oct3/4, but lack Sox2. Therefore, we tested whether overexpression of Sox2 enhances pluripotency and facilitates differentiation of cMABs in cardiovascular lineages. METHODS AND RESULTS: Lentiviral transduction of Sox2 (Sox-MABs) enhanced the capacity of cMABs to differentiate into endothelial cells and cardiomyocytes in vitro. Furthermore, the number of smooth muscle actin positive cells was higher in Sox-MABs. In addition, pluripotency of Sox-MABs was shown by demonstrating the generation of endodermal and ectodermal progenies. To test whether Sox-MABs may exhibit improved therapeutic potential, we injected Sox-MABs into nude mice after acute myocardial infarction. Four weeks after cell therapy with Sox-MABs, cardiac function was significantly improved compared to mice treated with control cMABs. Furthermore, cell therapy with Sox-MABs resulted in increased number of differentiated cardiomyocytes, endothelial cells, and smooth muscle cells in vivo. CONCLUSIONS: The complementation of Sox2 in Oct3/4-, Klf4-, and c-Myc-expressing cMABs enhanced the differentiation into all 3 cardiovascular lineages and improved the functional recovery after acute myocardial infarction.

Original languageEnglish
Pages (from-to)1290-1302
Number of pages13
JournalCirculation research
Volume106
Issue number7
DOIs
Publication statusPublished - Apr 1 2010

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Koyanagi, M., Iwasaki, M., Rupp, S., Tedesco, F. S., Yoon, C. H., Boeckel, J. N., Trauth, J., Schütz, C., Ohtani, K., Goetz, R., Iekushi, K., Bushoven, P., Momma, S., Mummery, C., Passier, R., Henschler, R., Akintuerk, H., Schranz, D., Urbich, C., ... Dimmeler, S. (2010). Sox2 Transduction enhances cardiovascular repair capacity of blood-derived mesoangioblasts. Circulation research, 106(7), 1290-1302. https://doi.org/10.1161/CIRCRESAHA.109.206045