Hematopoietic stem cells do not repair the infarcted mouse heart.
OBJECTIVE
Recent reports suggest that hematopoietic stem cells (HSC) can transdifferentiate into cardiomyoctes and contribute to myocardial regeneration after injury. This concept has recently been challenged by studies in which bone-marrow (BM)-derived cells do not acquire a cardiac phenotype after direct injection into ischemic myocardium.


METHODS
In this study, we analyzed the effect of increased circulating adult BM cells by stimulation with stem cell factor (SCF; 200 microg/kg/d for 7 days) and granulocyte-colony stimulating factor (G-CSF, 50 microg/kg/d for 7 days) or by peripheral delivery of isolated adult BM cells on morphological and hemodynamic parameters of mouse hearts 6 weeks after induction of chronic myocardial infarction (MI). All animals were splenectomized to prevent sequestration of BM cells 2 weeks prior to the induction of MI. Cytokine treatment was initiated either 3 days prior to or 6 h after MI. Isolated, either whole or by magnetic beads lineage-depleted BM cells were injected via a tail vein 6 h after MI.


RESULTS
Left and right ventricular (LV and RV) function revealed no improvement in any treatment group when compared to untreated MI animals at baseline resting conditions as well as after stimulation with norepinephrine (NE; 1, 5, 10, 25, 50, and 100 ng bolus i.v. in 10 microl each) as measured by catherization with ultraminiature 1.4 F tip pressure transducers 6 weeks after MI. Moreover, there was no sign of myocardial regeneration in histological or gene expression analyses.


CONCLUSIONS
Mobilization or i.v. injection of BM cells do not have a measurable effect on cardiac regeneration.
Deten
Alexander
A
Carl-Ludwig-Institute of Physiology, Leipzig University, Liebigstr. 27, D-04103 Leipzig, Germany. deta@medizin.uni-leipzig.de
Volz
Hans Christian
HC
Clamors
Sören
S
Leiblein
Sabine
S
Briest
Wilfried
W
Marx
Grit
G
Zimmer
Heinz-Gerd
HG
D000818:Animals; D004247:DNA / Q000032:analysis; D004562:Electrocardiography; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006412:Hematopoietic Stem Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009203:Myocardial Infarction / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D012038:Regeneration; D019089:Stem Cell Factor / Q000627:therapeutic use; D033581:Stem Cell Transplantation; D017211:Treatment Failure; D014998:Y Chromosome
D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D004247:DNA