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Abstract

Myocardial infarction leads to loss of tissue and impairment of cardiac performance. The remaining myocytes are unable to reconstitute the necrotic tissue, and the post-infarcted heart deteriorates with time1. Injury to a target organ is sensed by distant stem cells, which migrate to the site of damage and undergo alternate stem cell differentiation2,3,4,5; these events promote structural and functional repair6,7,8. This high degree of stem cell plasticity prompted us to test whether dead myocardium could be restored by transplanting bone marrow cells in infarcted mice. We sorted lineage-negative (Lin-) bone marrow cells from transgenic mice expressing enhanced green fluorescent protein9 by fluorescence-activated cell sorting on the basis of c-kit expression10. Shortly after coronary ligation, Lin- c-kitPOS cells were injected in the contracting wall bordering the infarct. Here we report that newly formed myocardium occupied 68% of the infarcted portion of the ventricle 9 days after transplanting the bone marrow cells. The developing tissue comprised proliferating myocytes and vascular structures. Our studies indicate that locally delivered bone marrow cells can generate de novo myocardium, ameliorating the outcome of coronary artery disease.

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Acknowledgements

We thank Dr S. Izumo for providing us with the Csx2.5 antibody. This work was supported by grants from the NIH. S.C. is supported by a fellowship from the Mario Negri Institute of Pharmacologic Research, Milan, Italy.

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Affiliations

  1. *Department of Medicine, New York Medical College, Valhalla, New York 10595, USA

    • Jan Kajstura
    • , Stefano Chimenti
    • , Igor Jakoniuk
    • , Baosheng Li
    • , Bernardo Nadal-Ginard
    • , Annarosa Leri
    •  & Piero Anversa
  2. †Hematopoiesis Section, Genetics and Molecular Biology Branch, NHGRI, and

    • Donald Orlic
    • , Stacie M. Anderson
    •  & David M. Bodine
  3. ‡Laboratory of Molecular Biology, NINDS, NIH, Bethesda, Maryland 20892, USA

    • James Pickel
    •  & Ronald McKay

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Correspondence to Piero Anversa.

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https://doi.org/10.1038/35070587

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