期刊
BIOMATERIALS
卷 142, 期 -, 页码 112-123出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2017.07.021
关键词
Human cardiac organoid; Human induced stem cell-derived cardiomyocyte; Coronary vasculogenesis; Development modeling; Regenerative medicine
资金
- National Institutes of Health [8P20 GM103444, U54 GM104941]
- Clemson University
- National Science Foundation [NSF - EPS-0903795]
- NIH Cardiovascular Training Grant [T32 HL007260]
- US Department of Veterans Affairs Merit Review [I01 BX002327]
- NIH-NIGMS [P30 GM103342]
Recent progress in human organoids has provided 3D tissue systems to model human development, diseases, as well as develop cell delivery systems for regenerative therapies. While direct differentiation of human embryoid bodies holds great promise for cardiac organoid production, intramyocardial cell organization during heart development provides biological foundation to fabricate human cardiac organoids with defined cell types. Inspired by the intramyocardial organization events in coronary vasculogenesis, where a diverse, yet defined, mixture of cardiac cell types self-organizes into functional myocardium in the absence of blood flow, we have developed a defined method to produce scaffold-free human cardiac organoids that structurally and functionally resembled the lumenized vascular network in the developing myocardium, supported hiPSC-CM development and possessed fundamental cardiac tissue-level functions. In particular, this development-driven strategy offers a robust, tunable system to examine the contributions of individual cell types, matrix materials and additional factors for developmental insight, biomimetic matrix composition to advance biomaterial design, tissue/organ-level drug screening, and cell therapy for heart repair. (C) 2017 Elsevier Ltd. All rights reserved.
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