Metabolic Maturation Media Improve Physiological Function of Human iPSC-Derived Cardiomyocytes

Dries A M Feyen; Wesley L McKeithan; Arne A N Bruyneel; Sean Spiering; Larissa Hörmann; Bärbel Ulmer; Hui Zhang; Francesca Briganti; Michaela Schweizer; Bence Hegyi; Zhandi Liao; Risto-Pekka Pölönen; Kenneth S Ginsburg; Chi Keung Lam; Ricardo Serrano; Christine Wahlquist; Alexander Kreymerman; Michelle Vu; Prashila L Amatya; Charlotta S Behrens; Sara Ranjbarvaziri; Renee G C Maas; Matthew Greenhaw; Daniel Bernstein; Joseph C Wu; Donald M Bers; Thomas Eschenhagen; Christian M Metallo; Mark Mercola

doi:10.1016/j.celrep.2020.107925

Metabolic Maturation Media Improve Physiological Function of Human iPSC-Derived Cardiomyocytes

Dries A M Feyen, Wesley L McKeithan, Arne A N Bruyneel, Sean Spiering, Larissa Hörmann, Bärbel Ulmer, Hui Zhang, Francesca Briganti, Michaela Schweizer, Bence Hegyi, Zhandi Liao, Risto-Pekka Pölönen, Kenneth S Ginsburg, Chi Keung Lam, Ricardo Serrano, Christine Wahlquist, Alexander Kreymerman, Michelle Vu, Prashila L Amatya, Charlotta S BehrensSara Ranjbarvaziri, Renee G C Maas, Matthew Greenhaw, Daniel Bernstein, Joseph C Wu, Donald M Bers, Thomas Eschenhagen, Christian M Metallo, Mark Mercola

Department of Experimental Cardiology

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have enormous potential for the study of human cardiac disorders. However, their physiological immaturity severely limits their utility as a model system and their adoption for drug discovery. Here, we describe maturation media designed to provide oxidative substrates adapted to the metabolic needs of human iPSC (hiPSC)-CMs. Compared with conventionally cultured hiPSC-CMs, metabolically matured hiPSC-CMs contract with greater force and show an increased reliance on cardiac sodium (Na+) channels and sarcoplasmic reticulum calcium (Ca2+) cycling. The media enhance the function, long-term survival, and sarcomere structures in engineered heart tissues. Use of the maturation media made it possible to reliably model two genetic cardiac diseases: long QT syndrome type 3 due to a mutation in the cardiac Na+ channel SCN5A and dilated cardiomyopathy due to a mutation in the RNA splicing factor RBM20. The maturation media should increase the fidelity of hiPSC-CMs as disease models.

Original language	English
Article number	107925
Journal	Cell Reports
Volume	32
Issue number	3
DOIs	https://doi.org/10.1016/j.celrep.2020.107925
Publication status	Published - 21 Jul 2020

Keywords

cardiomyocyte
dilated cardiomyopathy
disease modeling
engineered heart tissues
induced pluripotent stem cells
long QT syndrome 3
maturation
physiology

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PIIS2211124720309062Final published version, 4.42 MBLicence: CC BY-NC-ND

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Feyen, D. A. M., McKeithan, W. L., Bruyneel, A. A. N., Spiering, S., Hörmann, L., Ulmer, B., Zhang, H., Briganti, F., Schweizer, M., Hegyi, B., Liao, Z., Pölönen, R.-P., Ginsburg, K. S., Lam, C. K., Serrano, R., Wahlquist, C., Kreymerman, A., Vu, M., Amatya, P. L., ... Mercola, M. (2020). Metabolic Maturation Media Improve Physiological Function of Human iPSC-Derived Cardiomyocytes. Cell Reports, 32(3), Article 107925. https://doi.org/10.1016/j.celrep.2020.107925

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title = "Metabolic Maturation Media Improve Physiological Function of Human iPSC-Derived Cardiomyocytes",

abstract = "Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have enormous potential for the study of human cardiac disorders. However, their physiological immaturity severely limits their utility as a model system and their adoption for drug discovery. Here, we describe maturation media designed to provide oxidative substrates adapted to the metabolic needs of human iPSC (hiPSC)-CMs. Compared with conventionally cultured hiPSC-CMs, metabolically matured hiPSC-CMs contract with greater force and show an increased reliance on cardiac sodium (Na+) channels and sarcoplasmic reticulum calcium (Ca2+) cycling. The media enhance the function, long-term survival, and sarcomere structures in engineered heart tissues. Use of the maturation media made it possible to reliably model two genetic cardiac diseases: long QT syndrome type 3 due to a mutation in the cardiac Na+ channel SCN5A and dilated cardiomyopathy due to a mutation in the RNA splicing factor RBM20. The maturation media should increase the fidelity of hiPSC-CMs as disease models.",

keywords = "cardiomyocyte, dilated cardiomyopathy, disease modeling, engineered heart tissues, induced pluripotent stem cells, long QT syndrome 3, maturation, physiology",

author = "Feyen, {Dries A M} and McKeithan, {Wesley L} and Bruyneel, {Arne A N} and Sean Spiering and Larissa H{\"o}rmann and B{\"a}rbel Ulmer and Hui Zhang and Francesca Briganti and Michaela Schweizer and Bence Hegyi and Zhandi Liao and Risto-Pekka P{\"o}l{\"o}nen and Ginsburg, {Kenneth S} and Lam, {Chi Keung} and Ricardo Serrano and Christine Wahlquist and Alexander Kreymerman and Michelle Vu and Amatya, {Prashila L} and Behrens, {Charlotta S} and Sara Ranjbarvaziri and Maas, {Renee G C} and Matthew Greenhaw and Daniel Bernstein and Wu, {Joseph C} and Bers, {Donald M} and Thomas Eschenhagen and Metallo, {Christian M} and Mark Mercola",

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year = "2020",

month = jul,

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doi = "10.1016/j.celrep.2020.107925",

language = "English",

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Feyen, DAM, McKeithan, WL, Bruyneel, AAN, Spiering, S, Hörmann, L, Ulmer, B, Zhang, H, Briganti, F, Schweizer, M, Hegyi, B, Liao, Z, Pölönen, R-P, Ginsburg, KS, Lam, CK, Serrano, R, Wahlquist, C, Kreymerman, A, Vu, M, Amatya, PL, Behrens, CS, Ranjbarvaziri, S, Maas, RGC, Greenhaw, M, Bernstein, D, Wu, JC, Bers, DM, Eschenhagen, T, Metallo, CM & Mercola, M 2020, 'Metabolic Maturation Media Improve Physiological Function of Human iPSC-Derived Cardiomyocytes', Cell Reports, vol. 32, no. 3, 107925. https://doi.org/10.1016/j.celrep.2020.107925

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T1 - Metabolic Maturation Media Improve Physiological Function of Human iPSC-Derived Cardiomyocytes

AU - Feyen, Dries A M

AU - McKeithan, Wesley L

AU - Bruyneel, Arne A N

AU - Spiering, Sean

AU - Hörmann, Larissa

AU - Ulmer, Bärbel

AU - Zhang, Hui

AU - Briganti, Francesca

AU - Schweizer, Michaela

AU - Hegyi, Bence

AU - Liao, Zhandi

AU - Pölönen, Risto-Pekka

AU - Ginsburg, Kenneth S

AU - Lam, Chi Keung

AU - Serrano, Ricardo

AU - Wahlquist, Christine

AU - Kreymerman, Alexander

AU - Vu, Michelle

AU - Amatya, Prashila L

AU - Behrens, Charlotta S

AU - Ranjbarvaziri, Sara

AU - Maas, Renee G C

AU - Greenhaw, Matthew

AU - Bernstein, Daniel

AU - Wu, Joseph C

AU - Bers, Donald M

AU - Eschenhagen, Thomas

AU - Metallo, Christian M

AU - Mercola, Mark

PY - 2020/7/21

Y1 - 2020/7/21

N2 - Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have enormous potential for the study of human cardiac disorders. However, their physiological immaturity severely limits their utility as a model system and their adoption for drug discovery. Here, we describe maturation media designed to provide oxidative substrates adapted to the metabolic needs of human iPSC (hiPSC)-CMs. Compared with conventionally cultured hiPSC-CMs, metabolically matured hiPSC-CMs contract with greater force and show an increased reliance on cardiac sodium (Na+) channels and sarcoplasmic reticulum calcium (Ca2+) cycling. The media enhance the function, long-term survival, and sarcomere structures in engineered heart tissues. Use of the maturation media made it possible to reliably model two genetic cardiac diseases: long QT syndrome type 3 due to a mutation in the cardiac Na+ channel SCN5A and dilated cardiomyopathy due to a mutation in the RNA splicing factor RBM20. The maturation media should increase the fidelity of hiPSC-CMs as disease models.

AB - Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have enormous potential for the study of human cardiac disorders. However, their physiological immaturity severely limits their utility as a model system and their adoption for drug discovery. Here, we describe maturation media designed to provide oxidative substrates adapted to the metabolic needs of human iPSC (hiPSC)-CMs. Compared with conventionally cultured hiPSC-CMs, metabolically matured hiPSC-CMs contract with greater force and show an increased reliance on cardiac sodium (Na+) channels and sarcoplasmic reticulum calcium (Ca2+) cycling. The media enhance the function, long-term survival, and sarcomere structures in engineered heart tissues. Use of the maturation media made it possible to reliably model two genetic cardiac diseases: long QT syndrome type 3 due to a mutation in the cardiac Na+ channel SCN5A and dilated cardiomyopathy due to a mutation in the RNA splicing factor RBM20. The maturation media should increase the fidelity of hiPSC-CMs as disease models.

KW - cardiomyocyte

KW - dilated cardiomyopathy

KW - disease modeling

KW - engineered heart tissues

KW - induced pluripotent stem cells

KW - long QT syndrome 3

KW - maturation

KW - physiology

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U2 - 10.1016/j.celrep.2020.107925

DO - 10.1016/j.celrep.2020.107925

M3 - Article

C2 - 32697997

SN - 2211-1247

VL - 32

JO - Cell Reports

JF - Cell Reports

IS - 3

M1 - 107925

ER -

Metabolic Maturation Media Improve Physiological Function of Human iPSC-Derived Cardiomyocytes

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