Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion

Jan Kajstura, Marcello Rota, Brian Whang, Stefano Cascapera, Toru Hosoda, Claudia Bearzi, Daria Nurzynska, Hideko Kasahara, Elias Zias, Massimiliano Bonafé, Bernardo Nadal-Ginard, Daniele Torella, Angelo Nascimbene, Federico Quaini, Konrad Urbanek, Annarosa Leri, Piero Anversa

Research output: Contribution to journalArticle

Abstract

Recent studies in mice have challenged the ability of bone marrow cells (BMCs) to differentiate into myocytes and coronary vessels. The claim has also been made that BMCs acquire a cell phenotype different from the blood lineages only by fusing with resident cells. Technical problems exist in the induction of myocardial infarction and the successful injection of BMCs in the mouse heart. Similarly, the accurate analysis of the cell populations implicated in the regeneration of the dead tissue is complex and these factors together may account for the negative findings. In this study, we have implemented a simple protocol that can easily be reproduced and have reevaluated whether injection of BMCs restores the infarcted myocardium in mice and whether cell fusion is involved in tissue reconstitution. For this purpose, c-kit-positive BMCs were obtained from male transgenic mice expressing enhanced green fluorescence protein (EGFP). EGFP and the Y-chromosome were used as markers of the progeny of the transplanted cells in the recipient heart. By this approach, we have demonstrated that BMCs, when properly administrated in the infarcted heart, efficiently differentiate into myocytes and coronary vessels with no detectable differentiation into hemopoietic lineages. However, BMCs have no apparent paracrine effect on the growth behavior of the surviving myocardium. Within the infarct, in 10 days, nearly 4.5 million biochemically and morphologically differentiated myocytes together with coronary arterioles and capillary structures were generated independently of cell fusion. In conclusion, BMCs adopt the cardiac cell lineages and have an important therapeutic impact on ischemic heart failure.

Original languageEnglish
Pages (from-to)127-137
Number of pages11
JournalCirculation Research
Volume96
Issue number1
DOIs
Publication statusPublished - Jan 21 2005

Keywords

  • Cell fusion
  • Myocardial regeneration
  • Transdifferentiation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion'. Together they form a unique fingerprint.

  • Cite this

    Kajstura, J., Rota, M., Whang, B., Cascapera, S., Hosoda, T., Bearzi, C., Nurzynska, D., Kasahara, H., Zias, E., Bonafé, M., Nadal-Ginard, B., Torella, D., Nascimbene, A., Quaini, F., Urbanek, K., Leri, A., & Anversa, P. (2005). Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion. Circulation Research, 96(1), 127-137. https://doi.org/10.1161/01.RES.0000151843.79801.60