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Updated: Jun 23, 2026
Delayed Intramyocardial Delivery of Stem Cells after Ischemia Reperfusion Injury in a Murine Model
Published on: September 3, 2020
Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium
Leo Timmers1, Sai Kiang Lim, Fatih Arslan
1Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
Abstract:
Although paracrine effects of mesenchymal stem cells (MSCs) have been suggested previously, cardioprotection by human MSC secretions has never been demonstrated. Human MSC-conditioned medium (CM) was collected by following a clinically compliant protocol. In a porcine model of ischemia and reperfusion injury, intravenous and intracoronary MSC-CM treatment significantly reduced myocardial nuclear oxidative stress as determined by immunostaining for 8-hydroxy-2'-deoxyguanosine. In addition, expression levels of phospho-SMAD2 and active caspase 3 were diminished following CM treatment, suggesting that TGF-beta signaling and apoptosis were reduced. This was associated with a 60% reduction in infarct size and marked improvement of systolic and diastolic cardiac performance as assessed with echocardiography and pressure volume loops. Fractionation studies revealed that only the fraction of the CM containing products >1000 kDa (100-220 nm) provided cardioprotection in a mouse model of ischemia and reperfusion injury. This indicates that the responsible paracrine factor of human MSCs is likely a large complex rather than a single small molecule. These data identify human MSC-CM as a promising therapeutic option to reduce myocardial infarct size in patients with acute MI and suggest that the use of stem cell secretions could extend the applicability of stem cells for therapeutic purposes.
Insights
Human mesenchymal stem cell (MSC) secretions protect the heart from injury. This cell-free therapy, using MSC-conditioned medium (CM), significantly reduced heart attack size and improved cardiac function in preclinical models.
Area of Science:
- Regenerative Medicine
- Cardiovascular Research
- Cell Biology
Background:
- Mesenchymal stem cells (MSCs) are known for paracrine effects, but their secretions' cardioprotective potential remains unproven.
- Previous studies suggested paracrine mechanisms for MSCs, but direct evidence for cardioprotection via MSC secretions was lacking.
Purpose of the Study:
- To investigate the cardioprotective effects of human MSC secretions (conditioned medium, CM) in models of myocardial ischemia and reperfusion injury.
- To identify the nature of the cardioprotective factor(s) within MSC-CM.
Main Methods:
- Collected human MSC-conditioned medium (CM) using a clinically compliant protocol.
- Administered MSC-CM intravenously and intracoronarily in a porcine model of ischemia-reperfusion injury.
- Assessed myocardial oxidative stress, apoptosis, infarct size, and cardiac function (echocardiography, pressure volume loops).
- Fractionated CM to identify the molecular weight and size of cardioprotective components.
Main Results:
- MSC-CM treatment significantly reduced myocardial oxidative stress (8-hydroxy-2'-deoxyguanosine) and apoptosis (caspase 3, phospho-SMAD2).
- A 60% reduction in infarct size and marked improvement in systolic and diastolic cardiac function were observed.
- Cardioprotection was attributed to secreted factors >1000 kDa (100-220 nm), indicating a large complex rather than a small molecule.
Conclusions:
- Human MSC-conditioned medium (CM) demonstrates significant cardioprotection in ischemia-reperfusion injury models.
- MSC-CM reduces myocardial oxidative stress, apoptosis, infarct size, and improves cardiac function.
- This cell-free approach using MSC secretions offers a promising therapeutic strategy for acute myocardial infarction and expands stem cell therapy applications.
