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In Vitro Differentiation of Human Mesenchymal Stem Cells into Functional Cardiomyocyte-like Cells
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Functional Characterization and Comparison of Intercellular Communication in Stem Cell-Derived Cardiomyocytes
Irene C Marcu1,2, Ardo Illaste1, Pernilla Heuking3
1Department of Physiology, University of Bern, Bern, Switzerland.
Stem Cells (Dayton, Ohio)
|May 14, 2015
Summary
Pluripotent stem cell-derived cardiomyocytes (SC-CMs) show similar electrical properties to native heart cells but have significantly reduced intercellular communication. This poor coupling may hinder their use in cardiac repair strategies.
Area of Science:
- Cardiovascular Research
- Stem Cell Biology
- Regenerative Medicine
Background:
- The heart's limited self-repair capacity necessitates novel treatments.
- Pluripotent stem cell-derived cardiomyocytes (SC-CMs) are a promising therapeutic option for cardiac repair.
- Assessing SC-CMs' electrical properties and intercellular communication is crucial for their clinical application.
Purpose of the Study:
- To characterize the electrical properties and Ca(2+) signaling of single SC-CMs.
- To evaluate the intercellular coupling and gap junction function in SC-CM cell pairs.
- To compare SC-CMs with native neonatal and HL-1 cardiomyocytes.
Main Methods:
- Electrophysiological recordings and Ca(2+) imaging of single SC-CMs.
- Dye transfer assays and gap junction analysis in SC-CM cell pairs.
- Computational simulations to assess the impact of gap junction density.
Main Results:
- SC-CMs exhibited electrophysiological and Ca(2+) handling similar to native cardiomyocytes, despite cell population heterogeneity.
- Significantly diminished intercellular coupling was observed in SC-CMs compared to native cells.
- Reduced connexin expression in gap junctions of SC-CMs was confirmed, impairing signal transmission.
Conclusions:
- SC-CMs possess a cardiogenic electrophysiological profile but show impaired intercellular communication.
- Inadequate gap junction coupling limits functional integration and signal transmission of SC-CMs.
- These findings highlight critical considerations for utilizing SC-CMs in cardiac repair therapies.
