An in silico Study of Cardiac hiPSC Electronic Maturation by Dynamic Clamp

Sofia Botti; Chiara Bartolucci; Rolf Krause; Luca F. Pavarino; Stefano Severi

doi:10.1007/978-3-031-35302-4_18

An in silico Study of Cardiac hiPSC Electronic Maturation by Dynamic Clamp

Sofia Botti^*, Chiara Bartolucci, Rolf Krause, Luca F. Pavarino, Stefano Severi

^*Corresponding author for this work

Applied Mathematics and Computational Science

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution › peer-review

Abstract

Regenerative cardiology recently advanced in patient–specific medicine by employing somatic cells to derive pluripotent stem cells and differentiate them into cardiomyocytes. Resulting populations present an immature phenotype; the Dynamic Clamp technique is a popular experimental manipulation to induce electronic maturation towards an adult phenotype. In this work, we present a fully virtual framework to study this Dynamic Clamp technique, based on the injection of the inward-rectifier potassium current into the myocyte, taking into account six different current formulations. We investigate the effects of the current injection on the action potential morphology and on three specific biomarkers for different current percentages, and we compare resulting morphologies with the standard transmembrane potential profile of a human adult cardiomyocyte. The results of this quantitative analysis suggest that atrial–like potassium current formulations allow the cell to reach action potential features comparable with the ones of mature cells, preventing the cell to show a non physiological morphology.

Original language	English (US)
Title of host publication	Functional Imaging and Modeling of the Heart - 12th International Conference, FIMH 2023, Proceedings
Editors	Olivier Bernard, Patrick Clarysse, Nicolas Duchateau, Jacques Ohayon, Magalie Viallon
Publisher	Springer Science and Business Media Deutschland GmbH
Pages	175-183
Number of pages	9
ISBN (Print)	9783031353017
DOIs	https://doi.org/10.1007/978-3-031-35302-4_18
State	Published - 2023
Event	Functional Imaging and Modeling of the Heart - 12th International Conference, FIMH 2023, Proceedings - Lyon, France Duration: Jun 19 2023 → Jun 22 2023

Publication series

Name	Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Volume	13958 LNCS
ISSN (Print)	0302-9743
ISSN (Electronic)	1611-3349

Conference

Conference	Functional Imaging and Modeling of the Heart - 12th International Conference, FIMH 2023, Proceedings
Country/Territory	France
City	Lyon
Period	06/19/23 → 06/22/23

Keywords

Cardiac action potential morphology
hiPSC–CMs
Virtual dynamic clamp

ASJC Scopus subject areas

Theoretical Computer Science
General Computer Science

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/978-3-031-35302-4_18

Cite this

Botti, S., Bartolucci, C., Krause, R., Pavarino, L. F., & Severi, S. (2023). An in silico Study of Cardiac hiPSC Electronic Maturation by Dynamic Clamp. In O. Bernard, P. Clarysse, N. Duchateau, J. Ohayon, & M. Viallon (Eds.), Functional Imaging and Modeling of the Heart - 12th International Conference, FIMH 2023, Proceedings (pp. 175-183). (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics); Vol. 13958 LNCS). Springer Science and Business Media Deutschland GmbH. https://doi.org/10.1007/978-3-031-35302-4_18

Botti, Sofia ; Bartolucci, Chiara ; Krause, Rolf et al. / An in silico Study of Cardiac hiPSC Electronic Maturation by Dynamic Clamp. Functional Imaging and Modeling of the Heart - 12th International Conference, FIMH 2023, Proceedings. editor / Olivier Bernard ; Patrick Clarysse ; Nicolas Duchateau ; Jacques Ohayon ; Magalie Viallon. Springer Science and Business Media Deutschland GmbH, 2023. pp. 175-183 (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)).

@inproceedings{dbcd4f5375644cce9d692b4b155d1fae,

title = "An in silico Study of Cardiac hiPSC Electronic Maturation by Dynamic Clamp",

abstract = "Regenerative cardiology recently advanced in patient–specific medicine by employing somatic cells to derive pluripotent stem cells and differentiate them into cardiomyocytes. Resulting populations present an immature phenotype; the Dynamic Clamp technique is a popular experimental manipulation to induce electronic maturation towards an adult phenotype. In this work, we present a fully virtual framework to study this Dynamic Clamp technique, based on the injection of the inward-rectifier potassium current into the myocyte, taking into account six different current formulations. We investigate the effects of the current injection on the action potential morphology and on three specific biomarkers for different current percentages, and we compare resulting morphologies with the standard transmembrane potential profile of a human adult cardiomyocyte. The results of this quantitative analysis suggest that atrial–like potassium current formulations allow the cell to reach action potential features comparable with the ones of mature cells, preventing the cell to show a non physiological morphology.",

keywords = "Cardiac action potential morphology, hiPSC–CMs, Virtual dynamic clamp",

author = "Sofia Botti and Chiara Bartolucci and Rolf Krause and Pavarino, {Luca F.} and Stefano Severi",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.; Functional Imaging and Modeling of the Heart - 12th International Conference, FIMH 2023, Proceedings ; Conference date: 19-06-2023 Through 22-06-2023",

year = "2023",

doi = "10.1007/978-3-031-35302-4_18",

language = "English (US)",

isbn = "9783031353017",

series = "Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)",

publisher = "Springer Science and Business Media Deutschland GmbH",

pages = "175--183",

editor = "Olivier Bernard and Patrick Clarysse and Nicolas Duchateau and Jacques Ohayon and Magalie Viallon",

booktitle = "Functional Imaging and Modeling of the Heart - 12th International Conference, FIMH 2023, Proceedings",

address = "Germany",

}

Botti, S, Bartolucci, C, Krause, R, Pavarino, LF & Severi, S 2023, An in silico Study of Cardiac hiPSC Electronic Maturation by Dynamic Clamp. in O Bernard, P Clarysse, N Duchateau, J Ohayon & M Viallon (eds), Functional Imaging and Modeling of the Heart - 12th International Conference, FIMH 2023, Proceedings. Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), vol. 13958 LNCS, Springer Science and Business Media Deutschland GmbH, pp. 175-183, Functional Imaging and Modeling of the Heart - 12th International Conference, FIMH 2023, Proceedings, Lyon, France, 06/19/23. https://doi.org/10.1007/978-3-031-35302-4_18

An in silico Study of Cardiac hiPSC Electronic Maturation by Dynamic Clamp. / Botti, Sofia; Bartolucci, Chiara; Krause, Rolf et al.
Functional Imaging and Modeling of the Heart - 12th International Conference, FIMH 2023, Proceedings. ed. / Olivier Bernard; Patrick Clarysse; Nicolas Duchateau; Jacques Ohayon; Magalie Viallon. Springer Science and Business Media Deutschland GmbH, 2023. p. 175-183 (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics); Vol. 13958 LNCS).

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution › peer-review

TY - GEN

T1 - An in silico Study of Cardiac hiPSC Electronic Maturation by Dynamic Clamp

AU - Botti, Sofia

AU - Bartolucci, Chiara

AU - Krause, Rolf

AU - Pavarino, Luca F.

AU - Severi, Stefano

PY - 2023

Y1 - 2023

N2 - Regenerative cardiology recently advanced in patient–specific medicine by employing somatic cells to derive pluripotent stem cells and differentiate them into cardiomyocytes. Resulting populations present an immature phenotype; the Dynamic Clamp technique is a popular experimental manipulation to induce electronic maturation towards an adult phenotype. In this work, we present a fully virtual framework to study this Dynamic Clamp technique, based on the injection of the inward-rectifier potassium current into the myocyte, taking into account six different current formulations. We investigate the effects of the current injection on the action potential morphology and on three specific biomarkers for different current percentages, and we compare resulting morphologies with the standard transmembrane potential profile of a human adult cardiomyocyte. The results of this quantitative analysis suggest that atrial–like potassium current formulations allow the cell to reach action potential features comparable with the ones of mature cells, preventing the cell to show a non physiological morphology.

AB - Regenerative cardiology recently advanced in patient–specific medicine by employing somatic cells to derive pluripotent stem cells and differentiate them into cardiomyocytes. Resulting populations present an immature phenotype; the Dynamic Clamp technique is a popular experimental manipulation to induce electronic maturation towards an adult phenotype. In this work, we present a fully virtual framework to study this Dynamic Clamp technique, based on the injection of the inward-rectifier potassium current into the myocyte, taking into account six different current formulations. We investigate the effects of the current injection on the action potential morphology and on three specific biomarkers for different current percentages, and we compare resulting morphologies with the standard transmembrane potential profile of a human adult cardiomyocyte. The results of this quantitative analysis suggest that atrial–like potassium current formulations allow the cell to reach action potential features comparable with the ones of mature cells, preventing the cell to show a non physiological morphology.

KW - Cardiac action potential morphology

KW - hiPSC–CMs

KW - Virtual dynamic clamp

UR - http://www.scopus.com/inward/record.url?scp=85172728925&partnerID=8YFLogxK

U2 - 10.1007/978-3-031-35302-4_18

DO - 10.1007/978-3-031-35302-4_18

M3 - Conference contribution

AN - SCOPUS:85172728925

SN - 9783031353017

T3 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)

SP - 175

EP - 183

BT - Functional Imaging and Modeling of the Heart - 12th International Conference, FIMH 2023, Proceedings

A2 - Bernard, Olivier

A2 - Clarysse, Patrick

A2 - Duchateau, Nicolas

A2 - Ohayon, Jacques

A2 - Viallon, Magalie

PB - Springer Science and Business Media Deutschland GmbH

T2 - Functional Imaging and Modeling of the Heart - 12th International Conference, FIMH 2023, Proceedings

Y2 - 19 June 2023 through 22 June 2023

ER -

Botti S, Bartolucci C, Krause R, Pavarino LF, Severi S. An in silico Study of Cardiac hiPSC Electronic Maturation by Dynamic Clamp. In Bernard O, Clarysse P, Duchateau N, Ohayon J, Viallon M, editors, Functional Imaging and Modeling of the Heart - 12th International Conference, FIMH 2023, Proceedings. Springer Science and Business Media Deutschland GmbH. 2023. p. 175-183. (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)). doi: 10.1007/978-3-031-35302-4_18