Copyright © 2004, European Society of Cardiology
Hematopoietic stem cells do not repair the infarcted mouse heart
aCarl-Ludwig-Institute of Physiology, Leipzig University, Liebigstr. 27, D-04103 Leipzig, Germany
bDepartment of Hematology, Leipzig University, D-04103 Leipzig, Germany
* Corresponding author. Tel.: +49 341 9715307; fax.: +49 341 9715509. Email address: deta{at}medizin.uni-leipzig.de
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 µg/kg/d for 7 days) and granulocyte-colony stimulating factor (G-CSF, 50 µg/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 µl 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.
Conclusion: Mobilization or i.v. injection of BM cells do not have a measurable effect on cardiac regeneration.
KEYWORDS Infarction; Stem cells; Cell therapy; Hemodynamics; Heart failure
Time for primary review 28 days
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