Bone marrow cells regenerate infarcted myocardium.
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.
Orlic
D
D
Hematopoiesis Section, Genetics and Molecular Biology Branch, NHGRI, NIH, Bethesda, MD 20892, USA.
Kajstura
J
J
Chimenti
S
S
Jakoniuk
I
I
Anderson
S M
SM
Li
B
B
Pickel
J
J
McKay
R
R
Nadal-Ginard
B
B
Bodine
D M
DM
Leri
A
A
Anversa
P
P
D000818:Animals; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D018031:Connexin 43 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D049452:Green Fluorescent Proteins; D019394:Ki-67 Antigen / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D064326:MEF2 Transcription Factors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000628:therapy*; D009206:Myocardium / Q000166:cytology / Q000473:pathology*; D018006:Myogenic Regulatory Factors; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D018031:Connexin 43; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D008164:Luminescent Proteins; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D019009:Proto-Oncogene Proteins c-kit