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PMID: 11287958 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Bone marrow cells regenerate infarcted myocardium.

Nature ·Vol. 410 ·No. 6829 ·2001-04-05 ·Pages 701-5

Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P

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 time. Injury to a target organ is sensed by distant stem cells, which migrate to the site of damage and undergo alternate stem cell differentiation; these events promote structural and functional repair. 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 protein by fluorescence-activated cell sorting on the basis of c-kit expression. 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.

MeSH Terms
Animals Bone Marrow Transplantation Cell Differentiation Connexin 43/metabolism DNA-Binding Proteins/metabolism Female Green Fluorescent Proteins Ki-67 Antigen/metabolism Luminescent Proteins/metabolism MEF2 Transcription Factors Male Mice Mice, Inbred C57BL Mice, Transgenic Myocardial Infarction/therapy Myocardium/cytology,pathology Myogenic Regulatory Factors Proto-Oncogene Proteins c-kit/metabolism Transcription Factors/metabolism
Chemicals
Connexin 43 DNA-Binding Proteins Ki-67 Antigen Luminescent Proteins MEF2 Transcription Factors Myogenic Regulatory Factors Transcription Factors Green Fluorescent Proteins Proto-Oncogene Proteins c-kit
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Orlic D
Hematopoiesis Section, Genetics and Molecular Biology Branch, NHGRI, NIH, Bethesda, MD 20892, USA.
Kajstura J
Chimenti S
Jakoniuk I
Anderson S M
Li B
Pickel J
McKay R
Nadal-Ginard B
Bodine D M
Leri A
Anversa P
Article Info
Journal
Nature
Abbr.
Nature
ISSN
0028-0836
Published
2001-04-05
Pages
701-5
Language
English
Region
England
NLM ID
0410462
Subset
IM
Corrections
CommentIn
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