File Download
  Links for fulltext
     (May Require Subscription)

Article: Combinatorial Treatment of Human Cardiac Engineered Tissues With Biomimetic Cues Induces Functional Maturation as Revealed by Optical Mapping of Action Potentials and Calcium Transients

TitleCombinatorial Treatment of Human Cardiac Engineered Tissues With Biomimetic Cues Induces Functional Maturation as Revealed by Optical Mapping of Action Potentials and Calcium Transients
Authors
Keywordsmaturation
tissue engineering
action potential
calcium handling
triiodothyronine
Issue Date2020
PublisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/physiology/
Citation
Frontiers in Physiology, 2020, v. 11, p. article no. 165 How to Cite?
AbstractAlthough biomimetic stimuli, such as microgroove-induced alignment (μ), triiodothyronine (T3) induction, and electrical conditioning (EC), have been reported to promote maturation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), a systematic examination of their combinatorial effects on engineered cardiac tissue constructs and the underlying molecular pathways has not been reported. Herein, human embryonic stem cell-derived ventricular cardiomyocytes (hESC-VCMs) were used to generate a micro-patterned human ventricular cardiac anisotropic sheets (hvCAS) for studying the physiological effects of combinatorial treatments by a range of functional, calcium (Ca2+)-handling, and molecular analyses. High-resolution optical mapping showed that combined μ-T3-EC treatment of hvCAS increased the conduction velocity, anisotropic ratio, and proportion of mature quiescent-yet-excitable preparations by 2. 3-, 1. 8-, and 5-fold (>70%), respectively. Such electrophysiological changes could be attributed to an increase in inward sodium current density and a decrease in funny current densities, which is consistent with the observed up- and downregulated SCN1B and HCN2/4 transcripts, respectively. Furthermore, Ca2+-handling transcripts encoding for phospholamban (PLN) and sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) were upregulated, and this led to faster upstroke and decay kinetics of Ca2+-transients. RNA-sequencing and pathway mapping of T3-EC-treated hvCAS revealed that the TGF-β signaling was downregulated; the TGF-β receptor agonist and antagonist TGF-β1 and SB431542 partially reversed T3-EC induced quiescence and reduced spontaneous contractions, respectively. Taken together, we concluded that topographical cues alone primed cardiac tissue constructs for augmented electrophysiological and calcium handling by T3-EC. Not only do these studies improve our understanding of hPSC-CM biology, but the orchestration of these pro-maturational factors also improves the use of engineered cardiac tissues for in vitro drug screening and disease modeling.
Descriptioneid_2-s2.0-85082702535
Persistent Identifierhttp://hdl.handle.net/10722/288422
ISSN
2023 Impact Factor: 3.2
2023 SCImago Journal Rankings: 1.006
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWONG, AOT-
dc.contributor.authorWONG, N-
dc.contributor.authorGeng, L-
dc.contributor.authorChow, MZY-
dc.contributor.authorLee, EK-
dc.contributor.authorWu, H-
dc.contributor.authorKhine, M-
dc.contributor.authorKong, CW-
dc.contributor.authorCosta, KD-
dc.contributor.authorKeung, WD-
dc.contributor.authorCheung, YF-
dc.contributor.authorLi, RA-
dc.date.accessioned2020-10-05T12:12:40Z-
dc.date.available2020-10-05T12:12:40Z-
dc.date.issued2020-
dc.identifier.citationFrontiers in Physiology, 2020, v. 11, p. article no. 165-
dc.identifier.issn1664-042X-
dc.identifier.urihttp://hdl.handle.net/10722/288422-
dc.descriptioneid_2-s2.0-85082702535-
dc.description.abstractAlthough biomimetic stimuli, such as microgroove-induced alignment (μ), triiodothyronine (T3) induction, and electrical conditioning (EC), have been reported to promote maturation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), a systematic examination of their combinatorial effects on engineered cardiac tissue constructs and the underlying molecular pathways has not been reported. Herein, human embryonic stem cell-derived ventricular cardiomyocytes (hESC-VCMs) were used to generate a micro-patterned human ventricular cardiac anisotropic sheets (hvCAS) for studying the physiological effects of combinatorial treatments by a range of functional, calcium (Ca2+)-handling, and molecular analyses. High-resolution optical mapping showed that combined μ-T3-EC treatment of hvCAS increased the conduction velocity, anisotropic ratio, and proportion of mature quiescent-yet-excitable preparations by 2. 3-, 1. 8-, and 5-fold (>70%), respectively. Such electrophysiological changes could be attributed to an increase in inward sodium current density and a decrease in funny current densities, which is consistent with the observed up- and downregulated SCN1B and HCN2/4 transcripts, respectively. Furthermore, Ca2+-handling transcripts encoding for phospholamban (PLN) and sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) were upregulated, and this led to faster upstroke and decay kinetics of Ca2+-transients. RNA-sequencing and pathway mapping of T3-EC-treated hvCAS revealed that the TGF-β signaling was downregulated; the TGF-β receptor agonist and antagonist TGF-β1 and SB431542 partially reversed T3-EC induced quiescence and reduced spontaneous contractions, respectively. Taken together, we concluded that topographical cues alone primed cardiac tissue constructs for augmented electrophysiological and calcium handling by T3-EC. Not only do these studies improve our understanding of hPSC-CM biology, but the orchestration of these pro-maturational factors also improves the use of engineered cardiac tissues for in vitro drug screening and disease modeling.-
dc.languageeng-
dc.publisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/physiology/-
dc.relation.ispartofFrontiers in Physiology-
dc.rightsThis Document is Protected by copyright and was first published by Frontiers. All rights reserved. It is reproduced with permission.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectmaturation-
dc.subjecttissue engineering-
dc.subjectaction potential-
dc.subjectcalcium handling-
dc.subjecttriiodothyronine-
dc.titleCombinatorial Treatment of Human Cardiac Engineered Tissues With Biomimetic Cues Induces Functional Maturation as Revealed by Optical Mapping of Action Potentials and Calcium Transients-
dc.typeArticle-
dc.identifier.emailGeng, L: genglin@hku.hk-
dc.identifier.emailKeung, WD: wkeung@hku.hk-
dc.identifier.emailCheung, YF: xfcheung@hku.hk-
dc.identifier.emailLi, RA: ronaldli@hkucc.hku.hk-
dc.identifier.authorityKong, CW=rp01563-
dc.identifier.authorityKeung, WD=rp01887-
dc.identifier.authorityCheung, YF=rp00382-
dc.identifier.authorityLi, RA=rp01352-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3389/fphys.2020.00165-
dc.identifier.pmid32226389-
dc.identifier.pmcidPMC7080659-
dc.identifier.scopuseid_2-s2.0-85082702535-
dc.identifier.hkuros314947-
dc.identifier.volume11-
dc.identifier.spagearticle no. 165-
dc.identifier.epagearticle no. 165-
dc.identifier.isiWOS:000525665000001-
dc.publisher.placeSwitzerland-
dc.identifier.issnl1664-042X-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats