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Pluripotent Stem Cell Derived Cardiac Cells for Myocardial Repair
Published on: February 3, 2017
Interrogating functional integration between injected pluripotent stem cell-derived cells and surrogate cardiac
Hannah Song1, Charles Yoon, Steven J Kattman
1Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, Canada M5S 1A1.
Summary
Engineered heart tissue models effectively screened embryonic stem cell-derived cardiac progenitors (ESCs-CPs) for cardiac cell therapy. ESCs-CPs integrated into host tissue, enhancing cardiac contraction, unlike ESC-derived cardiomyocytes.
Area of Science:
- Regenerative Medicine
- Cardiovascular Biology
- Stem Cell Biology
Background:
- Myocardial infarction causes irreversible cardiomyocyte loss, leading to heart failure.
- Cell transplantation shows promise for cardiac repair but faces challenges in cell survival, engraftment, and functional integration.
- Embryonic stem cells (ESCs) can differentiate into cardiac progenitors (CPs) and cardiomyocytes (CMs), offering a potential cell source for therapy.
Purpose of the Study:
- To evaluate specific cell types and transplantation conditions for functional integration in cardiac cell therapy.
- To validate engineered heart tissue (EHT) as a model system for screening cardiac cell transplantation strategies.
- To assess the integration potential of ESC-derived CPs and CMs (ESC-CPs and ESC-CMs) within a host cardiac tissue environment.
Main Methods:
- Utilized engineered heart tissue (EHT) as a cardiac tissue model.
- Employed quantitative molecular and electrophysiological analyses to assess cell integration.
- Validated the analytical platform using neonatal mouse cardiomyocytes (nCMs) and cardiac fibroblasts (cFBs).
- Screened ESC-CMs and ESC-CPs for their integration potential.
Main Results:
- Injected cardiac fibroblasts (cFBs) impaired electrical signal propagation in EHT.
- Injected neonatal mouse cardiomyocytes (nCMs) improved EHT function.
- Purified ESC-CMs showed reduced electrophysiological integration, correlated with lower connexin 43 expression compared to nCMs.
- ESC-CPs demonstrated appropriate maturation and integration into EHT, enhancing contraction amplitude.
Conclusions:
- Engineered heart tissue (EHT) serves as an effective model system for accelerating cardiac cell therapy development.
- ESC-derived cardiac progenitors (ESC-CPs) show significant potential for functional integration and therapeutic benefit in cardiac repair.
- The study highlights the importance of cell type selection and maturation state for successful cardiac cell transplantation.
