Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion.
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.
Kajstura
Jan
J
Cardiovascular Research Institute, Department of Medicine, New York Medical College, Valhalla, NY 10595, USA. jan_kajstura@nymc.edu
Rota
Marcello
M
Whang
Brian
B
Cascapera
Stefano
S
Hosoda
Toru
T
Bearzi
Claudia
C
Nurzynska
Daria
D
Kasahara
Hideko
H
Zias
Elias
E
Bonafé
Massimiliano
M
Nadal-Ginard
Bernardo
B
Torella
Daniele
D
Nascimbene
Angelo
A
Quaini
Federico
F
Urbanek
Konrad
K
Leri
Annarosa
A
Anversa
Piero
P
D000818:Animals; D001160:Arterioles / Q000166:cytology; D016477:Artifacts; D001854:Bone Marrow Cells / Q000166:cytology*; D002196:Capillaries / Q000166:cytology; D002454:Cell Differentiation; D002459:Cell Fusion; D019070:Cell Lineage; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D017930:Genes, Reporter; D006085:Graft Survival; D049452:Green Fluorescent Proteins / Q000032:analysis; D006321:Heart / Q000502:physiology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015552:Injections, Intralesional; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000601:surgery*; D032383:Myocytes, Cardiac / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D009928:Organ Specificity; D019899:Paracrine Communication; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D012038:Regeneration; D033581:Stem Cell Transplantation; D016277:Ventricular Function, Left; D014998:Y Chromosome
C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D019009:Proto-Oncogene Proteins c-kit