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Updated: Jun 20, 2026
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Real-Time Measurements of Calcium and Contractility Parameters in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Published on: May 26, 2023
Spontaneous calcium oscillations regulate human cardiac progenitor cell growth
João Ferreira-Martins1, Carlos Rondon-Clavo, Derin Tugal
1Department of Anesthesia and Cardiovascular Division, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Circulation Research
|September 12, 2009
Summary
Calcium (Ca2+) oscillations in human cardiac progenitor cells (hCPCs) drive their cell cycle entry and expansion. This finding reveals a novel mechanism for cardiac repair and regeneration using progenitor cells.
Area of Science:
- Cardiovascular Biology
- Cellular and Molecular Medicine
- Regenerative Medicine
Background:
- The adult heart contains progenitor cells in myocardial niches, but their activation mechanisms are unknown.
- Understanding progenitor cell activation is crucial for cardiac repair strategies.
Purpose of the Study:
- To investigate the role of intracellular calcium (Ca2+) in the division and fate of c-kit-positive human cardiac progenitor cells (hCPCs).
- To explore the signaling pathways regulating Ca2+ dynamics in hCPCs.
Main Methods:
- Identified Ca2+ oscillations in hCPCs using live-cell imaging.
- Investigated the role of endoplasmic reticulum Ca2+ release (IP3Rs) and reuptake (SERCA) in hCPC Ca2+ dynamics.
- Assessed the impact of extracellular stimuli like ATP and histamine on Ca2+ oscillations.
- Determined the correlation between Ca2+ oscillations and cell cycle progression (5-bromodeoxyuridine incorporation).
- Evaluated the therapeutic potential of induced Ca2+ oscillations in hCPCs for myocardial infarction models in mice.
Main Results:
- Ca2+ oscillations were observed in hCPCs, independent of cardiomyocyte coupling or extracellular Ca2+.
- Inositol 1,4,5-triphosphate receptors (IP3Rs) and SERCA regulated these oscillations, with high expression in hCPCs.
- ATP and histamine significantly increased Ca2+ oscillation frequency by activating purinoceptors and histamine-1 receptors.
- Ca2+ oscillations were directly linked to hCPC cell cycle entry and proliferation.
- Pre-conditioning hCPCs with induced Ca2+ oscillations enhanced their engraftment and progeny generation in infarcted mouse hearts.
Conclusions:
- IP3R-mediated Ca2+ mobilization is a key regulator of human cardiac progenitor cell growth.
- Controlling Ca2+ oscillations in hCPCs enhances their regenerative potential for cardiac repair.
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