TitleMicroscale generation of cardiospheres promotes robust enrichment of cardiomyocytes derived from human pluripotent stem cells.
Publication TypeJournal Article
Year of Publication2014
AuthorsNguyen, DC, Hookway, TA, Wu, Q, Jha, R, Preininger, MK, Chen, X, Easley, CA, Spearman, P, Deshpande, SR, Maher, K, Wagner, MB, McDevitt, TC, Xu, C
JournalStem Cell Reports
Date PublishedAugust 2014

Cardiomyocytes derived from human pluripotent stem cells (hPSCs) are a promising cell source for regenerative medicine, disease modeling, and drug discovery, all of which require enriched cardiomyocytes, ideally ones with mature phenotypes. However, current methods are typically performed in 2D environments that produce immature cardiomyocytes within heterogeneous populations. Here, we generated 3D aggregates of cardiomyocytes (cardiospheres) from 2D differentiation cultures of hPSCs using microscale technology and rotary orbital suspension culture. Nearly 100% of the cardiospheres showed spontaneous contractility and synchronous intracellular calcium transients. Strikingly, from starting heterogeneous populations containing ∼10%-40% cardiomyocytes, the cell population within the generated cardiospheres featured ∼80%-100% cardiomyocytes, corresponding to an enrichment factor of up to 7-fold. Furthermore, cardiomyocytes from cardiospheres exhibited enhanced structural maturation in comparison with those from a parallel 2D culture. Thus, generation of cardiospheres represents a simple and robust method for enrichment of cardiomyocytes in microtissues that have the potential use in regenerative medicine as well as other applications.

Alternate JournalStem Cell Reports
PubMed ID25254340
PubMed Central IDPMC4175548
Grant ListR21HL118454 / HL / NHLBI NIH HHS / United States
R21 HL118454 / HL / NHLBI NIH HHS / United States
ULITR00454 / / PHS HHS / United States