Author 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.
Title Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion.
Journal Circ Res
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.
Volume 96(1)
Pages 127-37
Published 2005-1-7
DOI 10.1161/01.RES.0000151843.79801.60
PII 01.RES.0000151843.79801.60
PMID 15569828
MeSH Animals Arterioles / cytology Artifacts Bone Marrow Cells / cytology* Capillaries / cytology Cell Differentiation Cell Fusion Cell Lineage* Endothelial Cells / cytology Female Genes, Reporter Graft Survival Green Fluorescent Proteins / analysis Heart / physiology Hematopoietic Stem Cell Transplantation Humans Injections, Intralesional Male Mice Mice, Transgenic Myocardial Contraction Myocardial Infarction / surgery* Myocytes, Cardiac / cytology Myocytes, Smooth Muscle / cytology Organ Specificity Paracrine Communication Proto-Oncogene Proteins c-kit / analysis Regeneration Stem Cell Transplantation* Ventricular Function, Left Y Chromosome
IF 14.467
Times Cited 373
Mice RBRC01198