Usage Information
Citation Information: JCI Insight. 2021;6(10):e134368. https://doi.org/10.1172/jci.insight.134368.
Abstract
Human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) have been used extensively to model inherited heart diseases, but hiPSC-CM models of ischemic heart disease are lacking. Here, our objective was to generate an hiPSC-CM model of ischemic heart disease. To this end, hiPSCs were differentiated into functional hiPSC-CMs and then purified using either a simulated ischemia media or by using magnetic antibody-based purification targeting the nonmyocyte population for depletion from the cell population. Flow cytometry analysis confirmed that each purification approach generated hiPSC-CM cultures that had more than 94% cTnT+ cells. After purification, hiPSC-CMs were replated as confluent syncytial monolayers for electrophysiological phenotype analysis and protein expression by Western blotting. The phenotype of metabolic stress–selected hiPSC-CM monolayers recapitulated many of the functional and structural hallmarks of ischemic CMs, including elevated diastolic calcium, diminished calcium transient amplitude, prolonged action potential duration, depolarized resting membrane potential, hypersensitivity to chemotherapy-induced cardiotoxicity, depolarized mitochondrial membrane potential, depressed SERCA2a expression, reduced maximal oxygen consumption rate, and abnormal response to β1-adrenergic receptor stimulation. These findings indicate that metabolic selection of hiPSC-CMs generated cell populations with phenotype similar to what is well known to occur in the setting of ischemic heart failure and thus provide a opportunity for study of human ischemic heart disease.
Authors
Justin Davis, Ahmad Chouman, Jeffery Creech, Andre Monteiro da Rocha, Daniela Ponce-Balbuena, Eric N. Jimenez Vazquez, Ruthann Nichols, Andrey Lozhkin, Nageswara R. Madamanchi, Katherine F. Campbell, Todd J. Herron
Usage data is cumulative from November 2023 through November 2024.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 1,493 | 992 |
| 211 | 206 | |
| Figure | 687 | 25 |
| Supplemental data | 38 | 11 |
| Citation downloads | 70 | 0 |
| Totals | 2,499 | 1,234 |
| Total Views | 3,733 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
