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Intramyocardial Cell Delivery: Observations in Murine Hearts
Published on: January 24, 2014
CD271+ Human Mesenchymal Stem Cells Show Antiarrhythmic Effects in a Novel Murine Infarction Model
Haval Sadraddin1, Ralf Gaebel1, Anna Skorska1
1Reference- and Translation Center for Cardiac Stem Cell Therapy (RTC), Rostock University Medical Center, Department of Cardiac Surgery, Department Life, Light & Matter (LL&M), 18057 Rostock, Germany.
Background:
Ventricular arrhythmias (VA) are a common cause of sudden death after myocardial infarction (MI). Therefore, developing new therapeutic methods for the prevention and treatment of VA is of prime importance.
Methods:
Human bone marrow derived CD271+ mesenchymal stem cells (MSC) were tested for their antiarrhythmic effect. This was done through the development of a novel mouse model using an immunocompromised Rag2-/- γc-/- mouse strain subjected to myocardial "infarction-reinfarction". The mice underwent a first ischemia-reperfusion through the left anterior descending (LAD) artery closure for 45 minutes with a subsequent second permanent LAD ligation after seven days from the first infarct.
Results:
This mouse model induced various types of VA detected with continuous electrocardiogram (ECG) monitoring via implanted telemetry device. The immediate intramyocardial delivery of CD271+ MSC after the first MI significantly reduced VA induced after the second MI.
Conclusions:
In addition to the clinical relevance, more closely reflecting patients who suffer from severe ischemic heart disease and related arrhythmias, our new mouse model bearing reinfarction warrants the time required for stem cell engraftment and for the first time enables us to analyze and verify significant antiarrhythmic effects of human CD271+ stem cells in vivo.
Insights
Human mesenchymal stem cells (MSC) reduced dangerous ventricular arrhythmias after heart attack in a new mouse model. This study highlights MSCs as a potential therapy for preventing sudden cardiac death post-myocardial infarction.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Stem Cell Therapy
Background:
- Ventricular arrhythmias (VA) are a significant cause of sudden cardiac death following myocardial infarction (MI).
- Developing novel therapeutic strategies for VA prevention and treatment is crucial in cardiovascular medicine.
Purpose of the Study:
- To evaluate the antiarrhythmic potential of human bone marrow-derived CD271+ mesenchymal stem cells (MSC).
- To establish and validate a novel mouse model for studying VA post-myocardial infarction with reinfarction.
Main Methods:
- A new immunocompromised mouse model (Rag2-/- γc-/-) was developed, undergoing a two-stage myocardial infarction (ischemia-reperfusion followed by permanent ligation).
- Continuous electrocardiogram (ECG) monitoring via telemetry was used to detect VA.
- Intramyocardial delivery of CD271+ MSC was performed immediately after the first myocardial infarction.
Main Results:
- The novel mouse model successfully induced various types of VA.
- Immediate intramyocardial administration of CD271+ MSC significantly suppressed VA that occurred after the second infarction.
Conclusions:
- The reinfarction mouse model provides a clinically relevant platform for assessing stem cell therapies.
- This study demonstrates the significant in vivo antiarrhythmic efficacy of human CD271+ MSC in a post-myocardial infarction setting.

