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Updated: Aug 20, 2026
Ultrasound-Guided Induced Pluripotent Stem Cell-Derived Cardiomyocyte Implantation in Myocardial Infarcted Mice
Published on: March 30, 2022
Hematopoietic stem cells do not repair the infarcted mouse heart
Alexander Deten1, Hans Christian Volz, Sören Clamors
1Carl-Ludwig-Institute of Physiology, Leipzig University, Liebigstr. 27, D-04103 Leipzig, Germany. deta@medizin.uni-leipzig.de
Insights
Mobilizing or injecting bone marrow cells does not improve cardiac regeneration after heart attack. Studies show no significant changes in heart function or tissue repair in mice treated with stem cell factor and G-CSF, or with injected bone marrow cells.
Area of Science:
- Cardiovascular Research
- Stem Cell Biology
- Regenerative Medicine
Background:
- Hematopoietic stem cells (HSC) were previously thought to regenerate heart muscle.
- Recent studies challenge the concept of HSC transdifferentiation into cardiomyocytes after myocardial injury.
Purpose of the Study:
- To investigate the impact of increased circulating adult bone marrow (BM) cells on cardiac function and regeneration.
- To evaluate the effects of stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF) on myocardial infarction (MI) recovery.
- To assess the efficacy of direct injection of BM cells into ischemic myocardium.
Main Methods:
- Mice with induced chronic myocardial infarction (MI) were treated with SCF and G-CSF or injected with isolated BM cells.
- Animals were splenectomized to prevent BM cell sequestration.
- Cardiac function was assessed using catheterization, and myocardial regeneration was analyzed via histological and gene expression studies 6 weeks post-MI.
Main Results:
- No significant improvement in left and right ventricular function was observed in any treatment group compared to controls.
- Neither cytokine treatment nor BM cell injection led to enhanced cardiac repair or regeneration.
- Histological and gene expression analyses showed no signs of myocardial regeneration.
Conclusions:
- Mobilization of bone marrow cells through cytokine stimulation does not promote cardiac regeneration.
- Intravenous injection of bone marrow cells does not yield measurable benefits for cardiac repair after myocardial infarction.
- Current strategies involving BM cell manipulation show no therapeutic effect on heart regeneration.
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.
Conclusion:
Mobilization or i.v. injection of BM cells do not have a measurable effect on cardiac regeneration.
