Passive Stretch Induces Structural and Functional Maturation of Engineered Heart Muscle as Predicted by Computational Modeling

Stem Cells
Oscar J AbilezJoseph C Wu

Abstract

The ability to differentiate human pluripotent stem cells (hPSCs) into cardiomyocytes (CMs) makes them an attractive source for repairing injured myocardium, disease modeling, and drug testing. Although current differentiation protocols yield hPSC-CMs to >90% efficiency, hPSC-CMs exhibit immature characteristics. With the goal of overcoming this limitation, we tested the effects of varying passive stretch on engineered heart muscle (EHM) structural and functional maturation, guided by computational modeling. Human embryonic stem cells (hESCs, H7 line) or human induced pluripotent stem cells (IMR-90 line) were differentiated to hPSC-derived cardiomyocytes (hPSC-CMs) in vitro using a small molecule based protocol. hPSC-CMs were characterized by troponin+ flow cytometry as well as electrophysiological measurements. Afterwards, 1.2 × 106 hPSC-CMs were mixed with 0.4 × 106 human fibroblasts (IMR-90 line) (3:1 ratio) and type-I collagen. The blend was cast into custom-made 12-mm long polydimethylsiloxane reservoirs to vary nominal passive stretch of EHMs to 5, 7, or 9 mm. EHM characteristics were monitored for up to 50 days, with EHMs having a passive stretch of 7 mm giving the most consistent formation. Based on our initial macrosco...Continue Reading

References

Jan 13, 1997·The Journal of Cell Biology·R G PartonE Stang
Nov 6, 1998·Science·J A ThomsonJ M Jones
Mar 4, 2000·Biotechnology and Bioengineering·W H ZimmermannT Eschenhagen
Dec 18, 2004·Proceedings of the National Academy of Sciences of the United States of America·Milica RadisicGordana Vunjak-Novakovic
Jan 8, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Stig UrheimOtto A Smiseth
Apr 4, 2006·Nature Medicine·Wolfram-Hubertus ZimmermannThomas Eschenhagen
Jan 16, 2007·Circulation Research·Oren CaspiShulamit Levenberg
Sep 4, 2007·Biophysical Journal·R John Solaro
Nov 22, 2007·Science·Junying YuJames A Thomson
May 21, 2008·Handbook of Experimental Pharmacology·H H PatelP A Insel
Oct 29, 2008·Circulation·Raghava S VelagaletiRamachandran S Vasan
Dec 10, 2008·Tissue Engineering. Part a·Kelly R StevensCharles E Murry
Feb 14, 2009·Circulation Research·Jianhua ZhangTimothy J Kamp
Feb 18, 2010·Circulation·Rajiv R ChaturvediJonathan C Kentish
Jul 28, 2010·The New England Journal of Medicine·Alessandra MorettiKarl-Ludwig Laugwitz
Jan 18, 2011·Nature·Ilanit ItzhakiLior Gepstein
May 20, 2011·Nature·Michael A Laflamme, Charles E Murry
May 21, 2011·Circulation Research·Nathaniel L TullochCharles E Murry
Sep 29, 2011·Biophysical Journal·Oscar J AbilezEllen Kuhl
Oct 6, 2011·Cardiovascular Research·Matthias BrandenburgerAndreas Dendorfer
Apr 21, 2012·Science Translational Medicine·Ning SunJoseph C Wu
May 31, 2012·Proceedings of the National Academy of Sciences of the United States of America·Xiaojun LianSean P Palecek
Nov 7, 2012·Current Protocols in Cell Biology·Poh Loong SoongWolfram-Hubertus Zimmermann
May 30, 2013·Proceedings of the National Academy of Sciences of the United States of America·Megan L McCainKevin Kit Parker
Sep 14, 2013·Circulation Research·Lei YeJianyi Zhang
Oct 18, 2013·Science Translational Medicine·Kevin E HealyRobert M Nerem
Oct 22, 2013·Integrative Biology : Quantitative Biosciences From Nano to Macro·Frank B MyersOscar J Abilez
Nov 21, 2013·Proceedings of the National Academy of Sciences of the United States of America·Nimalan ThavandiranPeter W Zandstra
Dec 11, 2013·Proceedings of the National Academy of Sciences of the United States of America·Hailong WangVivek B Shenoy
Feb 1, 2014·Circulation Research·Xiulan YangCharles E Murry
Mar 4, 2014·American Journal of Physiology. Heart and Circulatory Physiology·Andrea StoehrArne Hansen
Apr 17, 2014·Journal of Molecular and Cellular Cardiology·Xiulan YangCharles E Murry

❮ Previous
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Citations

Nov 1, 2018·Annual Review of Pathology·Edward LauJoseph C Wu
Mar 28, 2019·Annual Review of Biomedical Engineering·Melanie Maurer, Jan Lammerding
Feb 25, 2020·Advanced Healthcare Materials·Chenyan WangZhen Ma
Apr 10, 2020·Circulation Research·Yuxuan Guo, William T Pu
Sep 18, 2020·Experimental Biology and Medicine·Keri Dame, Alexandre Js Ribeiro
Oct 1, 2020·Antioxidants & Redox Signaling·Kaveh RoshanbinfarFelix B Engel
Feb 10, 2019·Nature Reviews. Genetics·R Grant Rowe, George Q Daley
Oct 5, 2018·Frontiers in Cardiovascular Medicine·Michael J GreenbergTetsuro Wakatsuki
Apr 24, 2019·Nature Biomedical Engineering·Haodong ChenJoseph C Wu
Mar 25, 2019·Stem Cells International·Rosaria SantoroGiulio Pompilio
Apr 9, 2020·Frontiers in Cell and Developmental Biology·Razan Elfadil AhmedHideki Uosaki
Feb 2, 2019·World Journal of Stem Cells·Pranav Machiraju, Steven C Greenway
Oct 22, 2020·International Journal of Molecular Sciences·Lin JiangYigang Wang
Dec 2, 2020·Journal of Cardiovascular Translational Research·Ampadu O JacksonShiyin Long
Jul 7, 2020·Journal of Pharmacological and Toxicological Methods·Matthias GoßmannSonja Stoelzle-Feix
Oct 4, 2020·Journal of Molecular and Cellular Cardiology·Eric JabartJared M Churko
Jan 31, 2021·Tissue Engineering. Part C, Methods·Ignasi JorbaCarlijn V C Bouten
Feb 16, 2021·Journal of the American Heart Association·Caitlin HallDavor Pavlovic
Nov 21, 2020·Current Heart Failure Reports·Anton Deicher, Timon Seeger
Mar 10, 2021·European Heart Journal·Massimiliano GnecchiPeter J Schwartz
Feb 26, 2021·Pflügers Archiv : European journal of physiology·Kalina AndrysiakJózef Dulak
Apr 1, 2018·Journal of Molecular and Cellular Cardiology·Andrea LeonardNathan J Sniadecki
Jan 11, 2019·Acta Biomaterialia·F Sahli CostabalE Kuhl
Mar 19, 2021·Circulation Research·Giulia CampostriniChristine L Mummery
Mar 24, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Robin AugustinePablo Maureira
Feb 20, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Willem J de LangeJ Carter Ralphe
Apr 26, 2021·Journal of Molecular and Cellular Cardiology·Sangkyun ChoJoseph C Wu
Dec 19, 2020·Current Opinion in Pharmacology·Nino ChiricoPieterjan Dierickx
Jun 3, 2021·Npj Regenerative Medicine·Miguel F TenreiroMargarida Serra
Jul 25, 2021·International Journal of Molecular Sciences·Joseph AzarWassim Abou-Kheir
Aug 8, 2021·International Journal of Molecular Sciences·Jennifer ZhangHung-Fat Tse
Dec 19, 2020·Stem Cell Reports·Jeroen M SteinMilena Bellin
Mar 25, 2019·Advanced Drug Delivery Reviews·Tim MeyerWolfram-Hubertus Zimmermann

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