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Impact of hydrodynamics on iPSC-derived cardiomyocyte differentiation processes

Samaras, JJ; Abecasis, B; Serra, M; Ducci, A; Micheletti, M; (2018) Impact of hydrodynamics on iPSC-derived cardiomyocyte differentiation processes. Journal of Biotechnology , 287 pp. 18-27. 10.1016/j.jbiotec.2018.07.028. Green open access

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Abstract

Cardiomyocytes (CMs), derived from pluripotent stem cells (PSCs), have the potential to be used in cardiac repair. Addition of physical cues, such as electrical and mechanical stimulations, have proven to significantly effect morphology, density, cardiogenesis, maturity and functionality of differentiated CMs. This work combines rigorous fluid dynamics investigation and flow frequency analysis with iPSC differentiation experiments to identify and quantify the flow characteristics leading to a significant increase of differentiation yield. This is towards a better understanding of the physical relationship between frequency modulation and embryoid bodies suspension, and the development of dimensionless correlations applicable at larger scales. Laser Doppler Anemometry and Fast Fourier Transform analysis were used to identify characteristic flow frequencies under different agitation modes. Intermittent agitation resulted in a pattern of low intensity frequencies at reactor scale that could be controlled by varying three identified time components: rotational speed, interval and dwell times. A proof of concept biological study was undertaken, tuning the hydrodynamic environment through variation of dwell time based on the engineering study findings and a significant improvement in CM yield was obtained. This work introduces the concept of fine-tuning the physical hydrodynamic cues within a three-dimensional flow system to improve cardiomyocyte differentiation of iPSC.

Type: Article
Title: Impact of hydrodynamics on iPSC-derived cardiomyocyte differentiation processes
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jbiotec.2018.07.028
Publisher version: https://doi.org/10.1016/j.jbiotec.2018.07.028
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Cardiomyocyte differentiation, Hydrodynamics, FFT, Suspension dynamics, Induced pluripotent stem cells
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10062780
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