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Updated: Jul 14, 2026
In Vitro Differentiation of Human Mesenchymal Stem Cells into Functional Cardiomyocyte-like Cells
Published on: August 9, 2017
Differentiation in vivo of cardiac committed human embryonic stem cells in postmyocardial infarcted rats
André Tomescot1, Julia Leschik, Valérie Bellamy
1Institut National de la Santé et de la Recherche Médicale/Evry University Unité Mixte de Recherche 861, I-Stem, Association Française contre les Myopathies, 5, rue Desbrières, Evry 91030, France.
Insights
Human embryonic stem cells, when directed towards a cardiac lineage, demonstrated myocardial regenerative capacity after transplantation into infarcted rat hearts. These cardiac-specified stem cells successfully differentiated into cardiomyocytes without forming teratomas.
Area of Science:
- Stem Cell Biology
- Cardiovascular Research
- Regenerative Medicine
Background:
- Human embryonic stem (HES) cells can differentiate into cardiomyocytes in vitro.
- The potential for undifferentiated HES cells to regenerate myocardium in vivo remains largely unestablished.
- Investigating HES cell myocardial regenerative capacity is crucial for developing new cardiac therapies.
Purpose of the Study:
- To determine if cardiac-specified HES cells possess myocardial regenerative capacity after in vivo engraftment.
- To compare the efficacy of two HES cell lines (HUES-1 and I6) directed towards a cardiac lineage.
- To assess the differentiation and safety of transplanted HES cells in a rat myocardial infarction model.
Main Methods:
- Two HES cell lines were differentiated towards a cardiac lineage using bone morphogenetic protein-2 (BMP2) and SU5402.
- Gene expression of mesodermal and cardiac markers was analyzed using real-time polymerase chain reaction (PCR).
- Immunosuppressed rats with myocardial infarction received in-scar injections of HES cells or control medium, followed by analysis of cell differentiation and teratoma formation.
Main Results:
- Cardiac-specified HES cells expressed key mesodermal and cardiac genes (Tbx6, Isl1, FoxH1, Nkx2.5, Mef2c, alpha-actin).
- Human cells were detected in infarcted rat hearts 2 months post-transplantation and showed cardiomyocytic differentiation (anti-beta myosin expression).
- No teratomas were observed in the hearts or other organs of transplanted rats.
Conclusions:
- Cardiac-specified HES cells can differentiate into cardiomyocytes following transplantation into infarcted myocardium.
- These findings suggest that HES cells hold promise as an effective therapeutic candidate for myocardial regeneration.
- Further research into HES cell-based therapies could advance the treatment of heart disease.
Abstract:
Human embryonic stem (HES) cells can give rise to cardiomyocytes in vitro. However, whether undifferentiated HES cells also feature a myocardial regenerative capacity after in vivo engraftment has not been established yet. We compared two HES cell lines (HUES-1 and I6) that were specified toward a cardiac lineage by exposure to bone morphogenetic protein-2 (BMP2) and SU5402, a fibroblast growth factor receptor inhibitor. Real-time polymerase chain reaction (PCR) revealed that the cardiogenic inductive factor turned on expression of mesodermal and cardiac genes (Tbx6, Isl1, FoxH1, Nkx2.5, Mef2c, and alpha-actin). Thirty immunosuppressed rats underwent coronary artery ligation and, 2 weeks later, were randomized and received in-scar injections of either culture medium (controls) or BMP2 (+/-SU5402)-treated HES cells. After 2 months, human cells were detected by anti-human lamin immunostaining, and their cardiomyocytic differentiation was evidenced by their expression of cardiac markers by reverse transcription-PCR and immunofluorescence using an anti-beta myosin antibody. No teratoma was observed in hearts or any other organ of the body. The ability of cardiac-specified HES cells to differentiate along the cardiomyogenic pathway following transplantation into infarcted myocardium raises the hope that these cells might become effective candidates for myocardial regeneration.
