期刊
CIRCULATION RESEARCH
卷 122, 期 3, 页码 e5-e16出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.117.312067
关键词
arrhythmias, cardiac; humans; pluripotent stem cells; software; zebrafish
资金
- GlaxoSmithKline [35911 to 259146]
- ERC-AdG (European Research Council - Advanced Grant) STEMCARDIOVASC
- ZonMW (ZorgOnderzoek Nederland - Medische wetenschappen) MKMD (Meer Kennis met Minder Dieren)
- BHF (British Heart Foundation) [SP/15/9/31605, PG/14/59/31000, BIRAX 04BX14CDLG]
- ERC-AdG IndivuHeart
- DZHK (German Centre for Cardiovascular Research)
- ERC-StG (European Research Council - Starting Grant) StemCardioRisk
- Netherlands Organisation for Scientific Research [VIDI-917.15.303]
- British Heart Foundation [PG/14/59/31000, SP/15/9/31605, PG/09/027/27141] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [1379951] Funding Source: researchfish
- National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [NC/C013202/1] Funding Source: researchfish
- The British Council [04BX14CDLG] Funding Source: researchfish
Rationale: There are several methods to measure cardiomyocyte and muscle contraction, but these require customized hardware, expensive apparatus, and advanced informatics or can only be used in single experimental models. Consequently, data and techniques have been difficult to reproduce across models and laboratories, analysis is time consuming, and only specialist researchers can quantify data. Objective: Here, we describe and validate an automated, open-source software tool (MUSCLEMOTION) adaptable for use with standard laboratory and clinical imaging equipment that enables quantitative analysis of normal cardiac contraction, disease phenotypes, and pharmacological responses. Methods and Results: MUSCLEMOTION allowed rapid and easy measurement of movement from high-speed movies in (1) 1-dimensional in vitro models, such as isolated adult and human pluripotent stem cell-derived cardiomyocytes; (2) 2-dimensional in vitro models, such as beating cardiomyocyte monolayers or small clusters of human pluripotent stem cell-derived cardiomyocytes; (3) 3-dimensional multicellular in vitro or in vivo contractile tissues, such as cardiac organoids, engineered heart tissues, and zebrafish and human hearts. MUSCLEMOTION was effective under different recording conditions (bright-field microscopy with simultaneous patch-clamp recording, phase contrast microscopy, and traction force microscopy). Outcomes were virtually identical to the current gold standards for contraction measurement, such as optical flow, post deflection, edge-detection systems, or manual analyses. Finally, we used the algorithm to quantify contraction in in vitro and in vivo arrhythmia models and to measure pharmacological responses. Conclusions: Using a single open-source method for processing video recordings, we obtained reliable pharmacological data and measures of cardiac disease phenotype in experimental cell, animal, and human models.
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