Electro-mechanical conditioning of human iPSC-derived cardiomyocytes for translational research. (November 2017)

• Record Type: Journal Article
• Authors: Kroll, Katharina; Chabria, Mamta; Wang, Ken; Häusermann, Fabian; Schuler, Franz; Polonchuk, Liudmila
• Is Part Of: Progress in biophysics and molecular biology. Volume 130:Part B(2017)
• Page Start: 212
• Page End: 222
• Publication Date: 2017-11
• Subjects: Stem cell-derived cardiomyocytes -- Electro-mechanical stimulation -- Maturation -- Ca2+ handling -- Electrophysiology; Biophysics -- Periodicals; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular Biology -- Periodicals; Biophysique -- Périodiques; Biochimie -- Périodiques; 571.4
• DOI: 10.1016/j.pbiomolbio.2017.07.003
• Languages: English
• ISSNs: 0079-6107

Abstract

Abstract: Rationale: Impaired maturation of human iPSC-derived cardiomyocytes (hiPSC-CMs) currently limits their use in experimental research and further optimization is required to unlock their full potential. Objective: To push hiPSC-CMs towards maturation, we recapitulated the intrinsic cardiac properties by electro-mechanical stimulation and explored how these mimetic biophysical cues interplay and influence the cell behaviour. Methods and results: We introduced a novel device capable of applying synchronized electrical and mechanical stimuli to hiPSC-CM monolayers cultured on a PDMS membrane and evaluated effects of conditioning on cardiomyocyte structure and function. Human iPSC-CMs retained their cardiac phenotype and displayed adaptive structural responses to electrical (E), mechanical (M) and combined electro-mechanical (EM) stimuli, including enhanced membrane N-cadherin signal, stress-fiber formation and sarcomeric length shortening, most prominent under the EM stimulation. On the functional level, EM conditioning significantly reduced the transmembrane calcium current, resulting in a shift towards triangulation of intracellular calcium transients. In contrast, E and M stimulation applied independently increased the proportion of cells with L-Type calcium currents. In addition, calcium transients measured in the M-conditioned samples advanced to a more rectangular shape. Conclusion: The new methodology is a simple and elegant technique to systematically investigate and manipulate cardiomyocyte remodelling for translational applications. In the present study, we adjusted critical parameters to optimize a regimen for hiPSC-CM transformation. In the future, this technology will open up new avenues for electro-mechanical stimulation by allowing temporal and spatial control of stimuli which can be easily scaled up in complexity for cardiac development and disease modelling.