Abstract
Human induced pluripotent stem cells (hiPSCs) are among the most promising tools for regenerative myocardial therapy and in vitro modeling of cardiac disease; however, their full potential cannot be met without robust methods for differentiating them into cardiac-lineage cells. Here, we present novel protocols for generating hiPSC-derived cardiomyocytes (CMs), endothelial cells (ECs), and smooth muscle cells (SMCs) and for assembling them into a patch of human cardiac muscle (hCMP). The differentiation protocols can be completed in just a few weeks and are substantially more efficient than conventional methods, while the hCMP fabrication procedure produces a patch of clinically relevant size and incorporates a simple method for maturing the engineered tissue via mechanical stimulation. We also describe how the patch can be evaluated in a large-animal (swine) model of myocardial injury.
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Acknowledgments
This work was supported by the following funding sources: NIH RO1 HL 95077, HL114120, HL 131017, HL 138023, and UO1 HL134764.
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Gao, L., Zhang, J.(. (2021). Efficient Protocols for Fabricating a Large Human Cardiac Muscle Patch from Human Induced Pluripotent Stem Cells. In: Poss, K.D., Kühn, B. (eds) Cardiac Regeneration. Methods in Molecular Biology, vol 2158. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0668-1_14
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DOI: https://doi.org/10.1007/978-1-0716-0668-1_14
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