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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
Transdifferentiation of blood-derived human adult endothelial progenitor cells into functionally active
Cornel Badorff1, Ralf P Brandes, Rüdiger Popp
1Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Frankfurt, Germany.
Insights
Endothelial progenitor cells (EPCs) from healthy adults and coronary artery disease (CAD) patients can transform into functional cardiomyocytes. This cell-to-cell contact-mediated process holds promise for cardiac regeneration therapies.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Cell Biology
Background:
- Cell therapy is a potential strategy for cardiac regeneration.
- Recent research indicates progenitor cells can transdifferentiate into various cell types.
- The transdifferentiation capacity of endothelial progenitor cells (EPCs) remains largely unexplored.
Purpose of the Study:
- To investigate the transdifferentiation potential of endothelial progenitor cells (EPCs) into cardiomyocytes.
- To determine if EPCs from healthy donors and coronary artery disease (CAD) patients can differentiate into functional cardiac cells.
- To elucidate the mechanism mediating EPC transdifferentiation.
Main Methods:
- Endothelial progenitor cells (EPCs) were isolated from peripheral blood mononuclear cells of healthy adults and CAD patients.
- EPCs were co-cultured with rat cardiomyocytes and assessed for morphological and biochemical changes.
- Flow cytometry, immunocytochemistry, and calcium transient imaging were used to evaluate EPC differentiation and function.
- Gap junction communication was assessed using microinjection techniques.
Main Results:
- Co-culture with rat cardiomyocytes induced EPCs to adopt a cardiomyocyte-like morphology.
- A significant percentage of EPCs expressed cardiomyocyte-specific markers, including alpha-sarcomeric actinin.
- Transdifferentiated EPCs exhibited synchronized calcium transients with adjacent cardiomyocytes and formed gap junctions.
- EPC transdifferentiation was mediated by cell-to-cell contact, not cellular fusion.
Conclusions:
- Endothelial progenitor cells (EPCs) from both healthy individuals and CAD patients can transdifferentiate into functional cardiomyocytes in vitro.
- Cell-to-cell contact is the primary mechanism driving EPC transdifferentiation into cardiomyocytes.
- Autologous EPCs represent a promising cell source for therapeutic strategies aimed at cardiomyocyte regeneration in ischemic heart disease.
Background:
Further to promoting angiogenesis, cell therapy may be an approach for cardiac regeneration. Recent studies suggest that progenitor cells can transdifferentiate into other lineages. However, the transdifferentiation potential of endothelial progenitor cells (EPCs) is unknown.
Methods And Results:
EPCs were obtained from peripheral blood mononuclear cells of healthy adults or coronary artery disease (CAD) patients by cultivating with endothelial cell medium and growth factors. After 3 days, >95% of adherent cells were functionally and phenotypically EPCs. Diacetylated LDL-labeled EPCs were then cocultivated with rat cardiomyocytes for 6 days, resulting in significant increases of EPC cell length and size to a cardiomyocyte-like morphology. Biochemically, 9.94+/-1.39% and 5.04+/-1.09% of EPCs from healthy adults (n=15) or CAD patients (n=14, P<0.01 versus healthy adults), respectively, expressed alpha-sarcomeric actinin as measured by flow cytometry. Immunocytochemistry showed that human EPCs expressed alpha-sarcomeric actinin, cardiac troponin I (both with partial sarcomeric organization), atrial natriuretic peptide, and myocyte enhancer factor 2. Fluo 4 imaging demonstrated calcium transients synchronized with adjacent rat cardiomyocytes in transdifferentiated human EPCs. Single-cell microinjection of Lucifer yellow and calcein-AM labeling of cardiomyocytes demonstrated gap junctional communication between 51+/-7% of EPCs (16 hours after labeling, n=4) and cardiomyocytes. EPC transdifferentiation into cardiomyocytes was not observed with conditioned medium but in coculture with paraformaldehyde-fixed cardiomyocytes.
Conclusions:
EPCs from healthy volunteers and CAD patients can transdifferentiate in vitro into functionally active cardiomyocytes when cocultivated with rat cardiomyocytes. Cell-to-cell contact but not cellular fusion mediates EPC transdifferentiation. The therapeutic use of autologous EPCs may aid cardiomyocyte regeneration in patients with ischemic heart disease.
