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Updated: Jul 20, 2026

Delayed Intramyocardial Delivery of Stem Cells after Ischemia Reperfusion Injury in a Murine Model
Published on: September 3, 2020
Cellular cardiomyoplasty: improvement of left ventricular function correlates with the release of cardioactive
Henning Ebelt1, Mirco Jungblut, Ying Zhang
1Department of Medicine III, Martin Luther University, Halle, Germany.
Insights
Transplanted skeletal myoblasts and cardiomyocytes improve heart function after myocardial infarction. Their beneficial effects stem from releasing cardioactive cytokines, not cell integration.
Area of Science:
- Regenerative Medicine
- Cardiovascular Biology
- Cell Therapy
Background:
- Cardiac stem cell transplantation shows promise for treating myocardial infarction.
- The precise mechanisms of cardiac repair post-transplantation remain unclear.
- Cell differentiation into cardiomyocytes may not be the sole reparative pathway.
Purpose of the Study:
- To compare the therapeutic effects of skeletal myoblasts and ESC-derived cardiomyocytes after myocardial infarction.
- To investigate the role of cytokine release in cardiac repair mediated by transplanted cells.
- To elucidate the mechanisms underlying cell-based cardiac repair.
Main Methods:
- Implantation of skeletal myoblasts and ESC-derived cardiomyocytes into infarcted mouse hearts.
- Echocardiographic follow-up and histological analysis to assess cardiac function and tissue architecture.
- Measurement of cardioactive cytokine secretion by transplanted cells.
Main Results:
- Both cell types significantly improved left ventricle function and cardiac tissue architecture long-term.
- Skeletal myoblasts were not detected in infarcted hearts at 28 days post-transplantation.
- Transplanted cells secreted significant amounts of IL-1alpha, IL-6, TNF-beta, and oncostatin M, promoting cardiomyocyte survival and protein synthesis.
Conclusions:
- The beneficial effects of cell transplantation for cardiac repair are likely mediated by secreted cardioactive cytokines.
- Cell integration into the myocardium plays a limited role in the observed functional and morphological improvements.
- Cytokine release from transplanted cells represents a key mechanism in promoting cardiac regeneration.
Abstract:
A growing number of studies are reporting beneficial effects of the transplantation of alleged cardiac stem cells into diseased hearts after myocardial infarction. However, the mechanisms by which transplanted cells might help to promote repair of cardiac tissue are not understood and might involve processes different from the differentiation of transplanted cells into cardiomyocytes. We have compared the effects exerted by skeletal myoblasts (which are not able to form new cardiomyocytes) and ESC-derived cardiomyocytes after implantation into infarcted mouse hearts by echocardiographic follow-up and histological analysis and related these effects to the release of cardioactive cytokines. We found that both cell types led to a long-lasting improvement of left ventricle function and to an improvement of tissue architecture. Since no relevant amounts of myoblast-derived cells were present in infarcted hearts 28 days after transplantation, we investigated the release of cytokines from implanted cells both before and after transplantation into infarcted hearts. ESC-derived cardiomyocytes and myoblasts secreted substantial amounts of interleukin (IL)-1alpha, IL-6, tumor necrosis factor-beta, and oncostatin M, which strongly supported survival and protein synthesis of cultured cardiomyocytes. We postulate that the beneficial effects of the transplantation of myoblasts and cardiomyocytes on heart function and morphology only partially (if at all) depend on the integration of transplanted cells into the myocardium but do depend on the release of a complex blend of cardioactive cytokines.
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