Pivotal Role of Non-cardiomyocytes in Electromechanical and Therapeutic Potential of Induced Pluripotent Stem Cell-Derived Engineered Cardiac Tissue

Tissue Engineering. Part a
Hiroko IseokaYoshiki Sawa

Abstract

Although engineered cardiac tissues (ECTs) derived from induced pluripotent stem cells (iPSCs) are promising for myocardial regenerative therapy, the appropriate ratio of cardiomyocytes to non-cardiomyocytes is not fully understood. Here, we determined whether ECT-cell content is a key determinant of its structure/function, thereby affecting ECT therapeutic potential for advanced heart failure. Scaffold-free ECTs containing different ratios (25%, 50%, 70%, or 90%) of iPSC-derived cardiomyocytes were generated by magnetic-activated cell sorting by using cardiac-specific markers. Notably, ECTs showed synchronized spontaneous beating when cardiomyocytes constituted ≥50% of total cells, with the electrical-conduction velocity increasing depending on cardiomyocyte ratio; however, ECTs containing 90% cardiomyocytes failed to form stable structures. ECTs containing 25% or 50% cardiomyocytes predominantly expressed collagen and fibronectin, whereas ECTs containing 70% cardiomyocytes predominantly expressed laminin and exhibited the highest contractile/relaxation properties. Furthermore, transplantation of ECTs containing 50% or 70% cardiomyocytes into a rat chronic myocardial infarction model led to a more profound functional recovery ...Continue Reading

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Citations

Aug 1, 2018·Expert Opinion on Biological Therapy·Tilman ZieglerChristian Kupatt
Jul 7, 2018·Circulation Research·Jianyi ZhangGordana Vunjak-Novakovic
Jan 20, 2019·Biotechnology and Bioengineering·Bernardo AbecasisPaula M Alves
Dec 13, 2018·Current Drug Targets·Xiaotong WangYe Yuan
Mar 1, 2020·Tissue Engineering. Part C, Methods·Diwakar TuragaTodd C McDevitt
May 11, 2018·Nature Reviews. Cardiology·Philippe Menasché
Sep 21, 2018·Tissue Engineering. Part C, Methods·Katsuhisa MatsuuraTatsuya Shimizu
Nov 9, 2018·Frontiers in Cardiovascular Medicine·Maedeh ZamaniNgan F Huang
Dec 2, 2020·International Journal of Molecular Sciences·Junjun LiYoshiki Sawa
Nov 17, 2020·Frontiers in Cardiovascular Medicine·Dillon K JarrellJeffrey G Jacot
Nov 17, 2020·Frontiers in Bioengineering and Biotechnology·Philippe Menasché
Apr 4, 2021·International Journal of Molecular Sciences·Aleksandra NijakMaaike Alaerts
Jun 22, 2021·Frontiers in Bioengineering and Biotechnology·Mira ChingaleKe Huang
Aug 17, 2021·Journal of Biomedical Materials Research. Part a·Xinyue ChuXiong Xiao
Nov 27, 2021·Physiological Reports·Mohamadamin ForouzandehmehrMichelangelo Paci

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Methods Mentioned

BETA
confocal microscopy
flow-cytometry
PCR

Software Mentioned

Fluo
FluoVolt

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