Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease

Elisa Giacomelli; Viviana Meraviglia; Giulia Campostrini; Amy Cochrane; Xu Cao; Ruben W.J. van Helden; Ana Krotenberg Garcia; Maria Mircea; Sarantos Kostidis; Richard P. Davis; Berend J. van Meer; Carolina R. Jost; Abraham J. Koster; Hailiang Mei; David G. Míguez; Aat A. Mulder; Mario Ledesma-Terrón; Giulio Pompilio; Luca Sala; Daniela C.F. Salvatori; Roderick C. Slieker; Elena Sommariva; Antoine A.F. de Vries; Martin Giera; Stefan Semrau; Leon G.J. Tertoolen; Valeria V. Orlova; Milena Bellin; Christine L. Mummery

doi:https://doi.org/10.1016/j.stem.2020.05.004

Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease

Elisa Giacomelli, Viviana Meraviglia, Giulia Campostrini, Amy Cochrane, Xu Cao, Ruben W.J. van Helden, Ana Krotenberg Garcia, Maria Mircea, Sarantos Kostidis, Richard P. Davis, Berend J. van Meer, Carolina R. Jost, Abraham J. Koster, Hailiang Mei, David G. Míguez, Aat A. Mulder, Mario Ledesma-Terrón, Giulio Pompilio, Luca Sala, Daniela C.F. SalvatoriRoderick C. Slieker, Elena Sommariva, Antoine A.F. de Vries, Martin Giera, Stefan Semrau, Leon G.J. Tertoolen, Valeria V. Orlova, Milena Bellin, Christine L. Mummery

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

319 Citations (Scopus)

Abstract

Orlova, Bellin, Mummery, and colleagues combined three hiPSC-derived cardiac cell types in 3D microtissues. Cardiomyocytes matured structurally and functionally. Replacing healthy hiPSC-cardiac fibroblasts with patient fibroblasts recapitulated aspects of arrhythmogenic cardiomyopathy. Single-cell transcriptomics, electrophysiology, metabolomics, and ultrastructural analysis revealed roles for CX43 gap junctions and cAMP signaling in the tri-cell-type dialog.

Original language	English
Pages (from-to)	862-879.e11
Journal	Cell Stem Cell
Volume	26
Issue number	6
DOIs	https://doi.org/10.1016/j.stem.2020.05.004
Publication status	Published - 4 Jun 2020

Keywords

arrhythmogenic cardiomyopathy
cAMP
cardiac disease model
cardiac microtissue
cardiomyocyte maturation
cell-cell interaction
cyclic AMP
gap junction
human-induced-pluripotent-stem-cell-derived cardiac fibroblasts
human-induced-pluripotent-stem-cell-derived cardiomyocytes

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Giacomelli, E., Meraviglia, V., Campostrini, G., Cochrane, A., Cao, X., van Helden, R. W. J., Krotenberg Garcia, A., Mircea, M., Kostidis, S., Davis, R. P., van Meer, B. J., Jost, C. R., Koster, A. J., Mei, H., Míguez, D. G., Mulder, A. A., Ledesma-Terrón, M., Pompilio, G., Sala, L., ... Mummery, C. L. (2020). Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease. Cell Stem Cell, 26(6), 862-879.e11. https://doi.org/10.1016/j.stem.2020.05.004

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title = "Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease",

abstract = "Orlova, Bellin, Mummery, and colleagues combined three hiPSC-derived cardiac cell types in 3D microtissues. Cardiomyocytes matured structurally and functionally. Replacing healthy hiPSC-cardiac fibroblasts with patient fibroblasts recapitulated aspects of arrhythmogenic cardiomyopathy. Single-cell transcriptomics, electrophysiology, metabolomics, and ultrastructural analysis revealed roles for CX43 gap junctions and cAMP signaling in the tri-cell-type dialog.",

keywords = "arrhythmogenic cardiomyopathy, cAMP, cardiac disease model, cardiac microtissue, cardiomyocyte maturation, cell-cell interaction, cyclic AMP, gap junction, human-induced-pluripotent-stem-cell-derived cardiac fibroblasts, human-induced-pluripotent-stem-cell-derived cardiomyocytes",

author = "Elisa Giacomelli and Viviana Meraviglia and Giulia Campostrini and Amy Cochrane and Xu Cao and {van Helden}, {Ruben W.J.} and {Krotenberg Garcia}, Ana and Maria Mircea and Sarantos Kostidis and Davis, {Richard P.} and {van Meer}, {Berend J.} and Jost, {Carolina R.} and Koster, {Abraham J.} and Hailiang Mei and M{\'i}guez, {David G.} and Mulder, {Aat A.} and Mario Ledesma-Terr{\'o}n and Giulio Pompilio and Luca Sala and Salvatori, {Daniela C.F.} and Slieker, {Roderick C.} and Elena Sommariva and {de Vries}, {Antoine A.F.} and Martin Giera and Stefan Semrau and Tertoolen, {Leon G.J.} and Orlova, {Valeria V.} and Milena Bellin and Mummery, {Christine L.}",

year = "2020",

month = jun,

day = "4",

doi = "https://doi.org/10.1016/j.stem.2020.05.004",

language = "English",

volume = "26",

pages = "862--879.e11",

journal = "Cell Stem Cell",

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Giacomelli, E, Meraviglia, V, Campostrini, G, Cochrane, A, Cao, X, van Helden, RWJ, Krotenberg Garcia, A, Mircea, M, Kostidis, S, Davis, RP, van Meer, BJ, Jost, CR, Koster, AJ, Mei, H, Míguez, DG, Mulder, AA, Ledesma-Terrón, M, Pompilio, G, Sala, L, Salvatori, DCF, Slieker, RC, Sommariva, E, de Vries, AAF, Giera, M, Semrau, S, Tertoolen, LGJ, Orlova, VV, Bellin, M & Mummery, CL 2020, 'Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease', Cell Stem Cell, vol. 26, no. 6, pp. 862-879.e11. https://doi.org/10.1016/j.stem.2020.05.004

TY - JOUR

T1 - Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease

AU - Giacomelli, Elisa

AU - Meraviglia, Viviana

AU - Campostrini, Giulia

AU - Cochrane, Amy

AU - Cao, Xu

AU - van Helden, Ruben W.J.

AU - Krotenberg Garcia, Ana

AU - Mircea, Maria

AU - Kostidis, Sarantos

AU - Davis, Richard P.

AU - van Meer, Berend J.

AU - Jost, Carolina R.

AU - Koster, Abraham J.

AU - Mei, Hailiang

AU - Míguez, David G.

AU - Mulder, Aat A.

AU - Ledesma-Terrón, Mario

AU - Pompilio, Giulio

AU - Sala, Luca

AU - Salvatori, Daniela C.F.

AU - Slieker, Roderick C.

AU - Sommariva, Elena

AU - de Vries, Antoine A.F.

AU - Giera, Martin

AU - Semrau, Stefan

AU - Tertoolen, Leon G.J.

AU - Orlova, Valeria V.

AU - Bellin, Milena

AU - Mummery, Christine L.

PY - 2020/6/4

Y1 - 2020/6/4

N2 - Orlova, Bellin, Mummery, and colleagues combined three hiPSC-derived cardiac cell types in 3D microtissues. Cardiomyocytes matured structurally and functionally. Replacing healthy hiPSC-cardiac fibroblasts with patient fibroblasts recapitulated aspects of arrhythmogenic cardiomyopathy. Single-cell transcriptomics, electrophysiology, metabolomics, and ultrastructural analysis revealed roles for CX43 gap junctions and cAMP signaling in the tri-cell-type dialog.

AB - Orlova, Bellin, Mummery, and colleagues combined three hiPSC-derived cardiac cell types in 3D microtissues. Cardiomyocytes matured structurally and functionally. Replacing healthy hiPSC-cardiac fibroblasts with patient fibroblasts recapitulated aspects of arrhythmogenic cardiomyopathy. Single-cell transcriptomics, electrophysiology, metabolomics, and ultrastructural analysis revealed roles for CX43 gap junctions and cAMP signaling in the tri-cell-type dialog.

KW - arrhythmogenic cardiomyopathy

KW - cAMP

KW - cardiac disease model

KW - cardiac microtissue

KW - cardiomyocyte maturation

KW - cell-cell interaction

KW - cyclic AMP

KW - gap junction

KW - human-induced-pluripotent-stem-cell-derived cardiac fibroblasts

KW - human-induced-pluripotent-stem-cell-derived cardiomyocytes

UR - http://www.scopus.com/inward/record.url?scp=85085583148&partnerID=8YFLogxK

U2 - https://doi.org/10.1016/j.stem.2020.05.004

DO - https://doi.org/10.1016/j.stem.2020.05.004

M3 - Article

C2 - 32459996

SN - 1934-5909

VL - 26

SP - 862-879.e11

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 6

ER -

Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease

Abstract

Keywords

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