Opportunities and challenges in cardiac tissue engineering from an analysis of two decades of advances.
Journal
Nature biomedical engineering
ISSN: 2157-846X
Titre abrégé: Nat Biomed Eng
Pays: England
ID NLM: 101696896
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
13
05
2021
accepted:
08
03
2022
entrez:
28
4
2022
pubmed:
29
4
2022
medline:
30
4
2022
Statut:
ppublish
Résumé
Engineered human cardiac tissues facilitate progress in regenerative medicine, disease modelling and drug development. In this Perspective, we reflect on the most notable advances in cardiac tissue engineering from the past two decades by analysing pivotal studies and critically examining the most consequential developments. This retrospective analysis led us to identify key milestones and to outline a set of opportunities, along with their associated challenges, for the further advancement of engineered human cardiac tissues.
Identifiants
pubmed: 35478227
doi: 10.1038/s41551-022-00885-3
pii: 10.1038/s41551-022-00885-3
doi:
Types de publication
Journal Article
Review
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
327-338Subventions
Organisme : NHLBI NIH HHS
ID : F30 HL145921
Pays : United States
Organisme : NIBIB NIH HHS
ID : UH3 EB025765
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL076485
Pays : United States
Organisme : NIBIB NIH HHS
ID : P41 EB027062
Pays : United States
Informations de copyright
© 2022. Springer Nature Limited.
Références
Fine, B. & Vunjak-Novakovic, G. Shortcomings of animal models and the rise of engineered human cardiac tissue. ACS Biomater. Sci. Eng. 3, 1884–1897 (2017).
pubmed: 33440547
doi: 10.1021/acsbiomaterials.6b00662
Masashi, K. et al. Feasibility, safety, and therapeutic efficacy of human induced pluripotent stem cell-derived cardiomyocyte sheets in a porcine ischemic cardiomyopathy model. Circulation 126, S29–S37 (2012).
Weinberger, F. et al. Cardiac repair in guinea pigs with human engineered heart tissue from induced pluripotent stem cells. Sci. Transl. Med. 8, 363ra148 (2016).
pubmed: 27807283
doi: 10.1126/scitranslmed.aaf8781
Riegler, J. et al. Human engineered heart muscles engraft and survive long term in a rodent myocardial infarction model. Circ. Res. 117, 720–730 (2015).
pubmed: 26291556
pmcid: 4679370
doi: 10.1161/CIRCRESAHA.115.306985
Itzhaki, I. et al. Modelling the long QT syndrome with induced pluripotent stem cells. Nature 471, 225–229 (2011).
pubmed: 21240260
doi: 10.1038/nature09747
Tavakol, D. N., Fleischer, S. & Vunjak-Novakovic, G. Harnessing organs-on-a-chip to model tissue regeneration. Cell Stem Cell 28, 993–1015 (2021).
pubmed: 34087161
doi: 10.1016/j.stem.2021.05.008
Braam, S. R. et al. Prediction of drug-induced cardiotoxicity using human embryonic stem cell-derived cardiomyocytes. Stem Cell Res. 4, 107–116 (2010).
pubmed: 20034863
doi: 10.1016/j.scr.2009.11.004
Thomson, J. A. et al. Embryonic stem cell lines derived from human blastocysts. Science 282, 1145–1147 (1998).
pubmed: 9804556
doi: 10.1126/science.282.5391.1145
Itskovitz-Eldor, J. et al. Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers. Mol. Med. 6, 88–95 (2000).
pubmed: 10859025
pmcid: 1949933
doi: 10.1007/BF03401776
Kehat, I. et al. Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J. Clin. Invest. 108, 407–414 (2001).
pubmed: 11489934
pmcid: 209357
doi: 10.1172/JCI200112131
Mummery, C. et al. Differentiation of human embryonic stem cells to cardiomyocytes. Circulation 107, 2733–2740 (2003).
pubmed: 12742992
doi: 10.1161/01.CIR.0000068356.38592.68
Takahashi, K. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861–872 (2007).
pubmed: 18035408
doi: 10.1016/j.cell.2007.11.019
Zhang, J. et al. Functional cardiomyocytes derived from human induced pluripotent stem cells. Circ. Res. 104, e30–e41 (2009).
pubmed: 19213953
pmcid: 2741334
Gherghiceanu, M. et al. Cardiomyocytes derived from human embryonic and induced pluripotent stem cells: comparative ultrastructure. J. Cell. Mol. Med. 15, 2539–2551 (2011).
pubmed: 21883888
pmcid: 3822963
doi: 10.1111/j.1582-4934.2011.01417.x
Lee, J. H., Protze, S. I., Laksman, Z., Backx, P. H. & Keller, G. M. Human pluripotent stem cell-derived atrial and ventricular cardiomyocytes develop from distinct mesoderm populations. Cell Stem Cell 21, 179–194.e4 (2017).
pubmed: 28777944
doi: 10.1016/j.stem.2017.07.003
Protze, S. I. et al. Sinoatrial node cardiomyocytes derived from human pluripotent cells function as a biological pacemaker. Nat. Biotechnol. 35, 56–68 (2017).
pubmed: 27941801
doi: 10.1038/nbt.3745
Cyganek, L. et al. Deep phenotyping of human induced pluripotent stem cell-derived atrial and ventricular cardiomyocytes. JCI Insight 3, e99941 (2018).
Zhao, Y. et al. A platform for generation of chamber-specific cardiac tissues and disease modeling. Cell 176, 913–927.e18 (2019).
pubmed: 30686581
pmcid: 6456036
doi: 10.1016/j.cell.2018.11.042
Lemme, M. et al. Atrial-like engineered heart tissue: an in vitro model of the human atrium. Stem Cell Rep. 11, 1378–1390 (2018).
doi: 10.1016/j.stemcr.2018.10.008
Goldfracht, I. et al. Generating ring-shaped engineered heart tissues from ventricular and atrial human pluripotent stem cell-derived cardiomyocytes. Nat. Commun. 11, 75 (2020).
pubmed: 31911598
pmcid: 6946709
doi: 10.1038/s41467-019-13868-x
Zhou, P. & Pu, W. T. Recounting cardiac cellular composition. Circ. Res. 118, 368–370 (2016).
pubmed: 26846633
pmcid: 4755297
doi: 10.1161/CIRCRESAHA.116.308139
Tian, Y & Morrisey, E. Importance of myocyte-nonmyocyte interactions in cardiac development and disease. Circ. Res. 110, 1023–1034 (2012).
pubmed: 22461366
pmcid: 3366271
doi: 10.1161/CIRCRESAHA.111.243899
Iyer, D. et al. Robust derivation of epicardium and its differentiated smooth muscle cell progeny from human pluripotent stem cells. Development 142, 1528–1541 (2015).
pubmed: 25813541
pmcid: 4392600
Bao, X. et al. Long-term self-renewing human epicardial cells generated from pluripotent stem cells under defined xeno-free conditions. Nat. Biomed. Eng. 1, 0003 (2016).
Zhang, J. et al. Functional cardiac fibroblasts derived from human pluripotent stem cells via second heart field progenitors. Nat. Commun. 10, 2238 (2019).
pubmed: 31110246
pmcid: 6527555
doi: 10.1038/s41467-019-09831-5
Zhang, H. et al. Generation of quiescent cardiac fibroblasts from human induced pluripotent stem cells for in vitro modeling of cardiac fibrosis. Circ. Res. 125, 552–566 (2019).
pubmed: 31288631
pmcid: 6768436
doi: 10.1161/CIRCRESAHA.119.315491
Moretti, A. et al. Multipotent embryonic Isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell 127, 1151–1165 (2006).
pubmed: 17123592
doi: 10.1016/j.cell.2006.10.029
Palpant, N. J. et al. Inhibition of β-catenin signaling respecifies anterior-like endothelium into beating human cardiomyocytes. Development 142, 3198–3209 (2015).
pubmed: 26153229
pmcid: 4582173
Giacomelli, E. et al. Three-dimensional cardiac microtissues composed of cardiomyocytes and endothelial cells co-differentiated from human pluripotent stem cells. Development 144, 1008–1017 (2017).
pubmed: 28279973
pmcid: 5358113
Palpant, N. J. et al. Generating high-purity cardiac and endothelial derivatives from patterned mesoderm using human pluripotent stem cells. Nat. Protoc. 12, 15–31 (2017).
pubmed: 27906170
doi: 10.1038/nprot.2016.153
Passier, R. et al. Increased cardiomyocyte differentiation from human embryonic stem cells in serum-free cultures. Stem Cells 23, 772–780 (2005).
pubmed: 15917473
doi: 10.1634/stemcells.2004-0184
Burridge, P. W. et al. A universal system for highly efficient cardiac differentiation of human induced pluripotent stem cells that eliminates interline variability. PLoS ONE 6, e18293 (2011).
pubmed: 21494607
pmcid: 3072973
doi: 10.1371/journal.pone.0018293
Freund, C. et al. Insulin redirects differentiation from cardiogenic mesoderm and endoderm to neuroectoderm in differentiating human embryonic stem cells. Stem Cells 26, 724–733 (2008).
pubmed: 18096723
doi: 10.1634/stemcells.2007-0617
Cao, N. et al. Ascorbic acid enhances the cardiac differentiation of induced pluripotent stem cells through promoting the proliferation of cardiac progenitor cells. Cell Res. 22, 219–236 (2012).
pubmed: 22143566
doi: 10.1038/cr.2011.195
Kattman, S. J. et al. Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines. Cell Stem Cell 8, 228–240 (2011).
pubmed: 21295278
doi: 10.1016/j.stem.2010.12.008
Lian, X. et al. Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc. Natl Acad. Sci. USA 109, E1848–E1857 (2012).
pubmed: 22645348
pmcid: 3390875
doi: 10.1073/pnas.1200250109
Burridge, P. W. et al. Chemically defined and small molecule-based generation of human cardiomyocytes. Nat. Methods 11, 855–860 (2014).
pubmed: 24930130
pmcid: 4169698
doi: 10.1038/nmeth.2999
Matsuura, K. et al. Creation of human cardiac cell sheets using pluripotent stem cells. Biochem. Biophys. Res. Commun. 425, 321–327 (2012).
pubmed: 22842572
doi: 10.1016/j.bbrc.2012.07.089
Hamad, S. et al. Generation of human induced pluripotent stem cell-derived cardiomyocytes in 2D monolayer and scalable 3D suspension bioreactor cultures with reduced batch-to-batch variations. Theranostics 9, 7222–7238 (2019).
pubmed: 31695764
pmcid: 6831300
doi: 10.7150/thno.32058
Ashok, P., Parikh, A., Du, C. & Tzanakakis, E. S. Xenogeneic-free system for biomanufacturing of cardiomyocyte progeny from human pluripotent stem cells. Front. Bioeng. Biotechnol. 8, 571425 (2020).
pubmed: 33195131
pmcid: 7644809
doi: 10.3389/fbioe.2020.571425
Buikema, J. W. et al. Wnt activation and reduced cell-cell contact synergistically induce massive expansion of functional human ipsc-derived cardiomyocytes. Cell Stem Cell 27, 50–63.e5 (2020).
pubmed: 32619518
pmcid: 7334437
doi: 10.1016/j.stem.2020.06.001
Xu, C., Police, S., Rao, N. & Carpenter, M. K. Characterization and enrichment of cardiomyocytes derived from human embryonic stem cells. Circ. Res. 91, 501–508 (2002).
pubmed: 12242268
doi: 10.1161/01.RES.0000035254.80718.91
Huber, I. et al. Identification and selection of cardiomyocytes during human embryonic stem cell differentiation. FASEB J. 21, 2551–2563 (2007).
pubmed: 17435178
doi: 10.1096/fj.05-5711com
Anderson, D. et al. Transgenic enrichment of cardiomyocytes from human embryonic stem cells. Mol. Ther. 15, 2027–2036 (2007).
pubmed: 17895862
doi: 10.1038/sj.mt.6300303
Dubois, N. C. et al. SIRPA is a specific cell-surface marker for isolating cardiomyocytes derived from human pluripotent stem cells. Nat. Biotechnol. 29, 1011–1018 (2011).
pubmed: 22020386
pmcid: 4949030
doi: 10.1038/nbt.2005
Tohyama, S. et al. Distinct metabolic flow enables large-scale purification of mouse and human pluripotent stem cell-derived cardiomyocytes. Cell Stem Cell 12, 127–137 (2013).
pubmed: 23168164
doi: 10.1016/j.stem.2012.09.013
Mannhardt, I. et al. Comparison of 10 control hPSC lines for drug screening in an engineered heart tissue format. Stem Cell Rep. 15, 983–998 (2020).
doi: 10.1016/j.stemcr.2020.09.002
He, J.-Q., Ma, Y., Lee, Y., Thomson, J. A. & Kamp, T. J. Human embryonic stem cells develop into multiple types of cardiac myocytes. Circ. Res. 93, 32–39 (2003).
pubmed: 12791707
doi: 10.1161/01.RES.0000080317.92718.99
van den Berg, C. W. et al. Transcriptome of human foetal heart compared with cardiomyocytes from pluripotent stem cells. Development 142, 3231–3238 (2015).
pubmed: 26209647
Robertson, C., Tran, D. D. & George, S. C. Concise review: maturation phases of human pluripotent stem cell-derived cardiomyocytes. Stem Cells 31, 829–837 (2013).
pubmed: 23355363
doi: 10.1002/stem.1331
Zhang, D. et al. Tissue-engineered cardiac patch for advanced functional maturation of human ESC-derived cardiomyocytes. Biomaterials 34, 5813–5820 (2013).
pubmed: 23642535
pmcid: 3660435
doi: 10.1016/j.biomaterials.2013.04.026
Chun, Y. W. et al. Combinatorial polymer matrices enhance in vitro maturation of human induced pluripotent stem cell-derived cardiomyocytes. Biomaterials 67, 52–64 (2015).
pubmed: 26204225
pmcid: 4550551
doi: 10.1016/j.biomaterials.2015.07.004
Tiburcy, M. et al. Defined engineered human myocardium with advanced maturation for applications in heart failure modeling and repair. Circulation 135, 1832–1847 (2017).
pubmed: 28167635
pmcid: 5501412
doi: 10.1161/CIRCULATIONAHA.116.024145
Majid, Q. A. et al. Natural biomaterials for cardiac tissue engineering: a highly biocompatible solution. Front. Cardiovasc. Med. 7, 554597 (2020).
pubmed: 33195451
pmcid: 7644890
doi: 10.3389/fcvm.2020.554597
Branco, M. A. et al. Transcriptomic analysis of 3D cardiac differentiation of human induced pluripotent stem cells reveals faster cardiomyocyte maturation compared to 2D culture. Sci. Rep. 9, 9229 (2019).
pubmed: 31239450
pmcid: 6592905
doi: 10.1038/s41598-019-45047-9
Chen, F.-M. & Liu, X. Advancing biomaterials of human origin for tissue engineering. Prog. Polym. Sci. 53, 86–168 (2016).
pubmed: 27022202
doi: 10.1016/j.progpolymsci.2015.02.004
Kharaziha, M. et al. PGS:gelatin nanofibrous scaffolds with tunable mechanical and structural properties for engineering cardiac tissues. Biomaterials 34, 6355–6366 (2013).
pubmed: 23747008
pmcid: 3685203
doi: 10.1016/j.biomaterials.2013.04.045
Wu, Y., Wang, L., Guo, B. & Ma, P. X. Interwoven aligned conductive nanofiber yarn/hydrogel composite scaffolds for engineered 3D cardiac anisotropy. ACS Nano 11, 5646–5659 (2017).
pubmed: 28590127
doi: 10.1021/acsnano.7b01062
Ashtari, K. et al. Electrically conductive nanomaterials for cardiac tissue engineering. Adv. Drug Deliv. Rev. 144, 162–179 (2019).
pubmed: 31176755
pmcid: 6784829
doi: 10.1016/j.addr.2019.06.001
Zhao, Y. et al. Engineering microenvironment for human cardiac tissue assembly in heart-on-a-chip platform. Matrix Biol. 85–86, 189–204 (2020).
pubmed: 30981898
doi: 10.1016/j.matbio.2019.04.001
Breckwoldt, K. et al. Differentiation of cardiomyocytes and generation of human engineered heart tissue. Nat. Protoc. 12, 1177–1197 (2017).
pubmed: 28492526
doi: 10.1038/nprot.2017.033
Ronaldson-Bouchard, K. et al. Engineering of human cardiac muscle electromechanically matured to an adult-like phenotype. Nat. Protoc. 14, 2781–2817 (2019).
pubmed: 31492957
pmcid: 7195192
doi: 10.1038/s41596-019-0189-8
Schwach, V. & Passier, R. Native cardiac environment and its impact on engineering cardiac tissue. Biomater. Sci. 7, 3566–3580 (2019).
pubmed: 31338495
doi: 10.1039/C8BM01348A
Fong, A. H. et al. Three-dimensional adult cardiac extracellular matrix promotes maturation of human induced pluripotent stem cell-derived cardiomyocytes. Tissue Eng. Part A 22, 1016–1025 (2016).
pubmed: 27392582
pmcid: 4991595
doi: 10.1089/ten.tea.2016.0027
Rai, R. et al. Biomimetic poly(glycerol sebacate) (PGS) membranes for cardiac patch application. Mater. Sci. Eng. C Mater. Biol. Appl. 33, 3677–3687 (2013).
pubmed: 23910264
doi: 10.1016/j.msec.2013.04.058
Park, H., Radisic, M., Lim, J. O., Chang, B. H. & Vunjak-Novakovic, G. A novel composite scaffold for cardiac tissue engineering. In Vitro Cell. Dev. Biol. Anim. 41, 188–196 (2005).
pubmed: 16223333
doi: 10.1290/0411071.1
Xu, G. et al. Injectable biodegradable hybrid hydrogels based on thiolated collagen and oligo(acryloyl carbonate)–poly(ethylene glycol)–oligo(acryloyl carbonate) copolymer for functional cardiac regeneration. Acta Biomater. 15, 55–64 (2015).
pubmed: 25545323
doi: 10.1016/j.actbio.2014.12.016
Ketabat, F., Karkhaneh, A., Mehdinavaz Aghdam, R. & Hossein Ahmadi Tafti, S. Injectable conductive collagen/alginate/polypyrrole hydrogels as a biocompatible system for biomedical applications. J. Biomater. Sci. Polym. Ed. 28, 794–805 (2017).
pubmed: 28278043
doi: 10.1080/09205063.2017.1302314
Roshanbinfar, K. et al. Electroconductive biohybrid hydrogel for enhanced maturation and beating properties of engineered cardiac tissues. Adv. Funct. Mater. 28, 1803951 (2018).
doi: 10.1002/adfm.201803951
Sengupta, D. & Heilshorn, S. C. Protein-engineered biomaterials: highly tunable tissue engineering scaffolds. Tissue Eng. Part B Rev. 16, 285–293 (2010).
pubmed: 20141386
doi: 10.1089/ten.teb.2009.0591
Farajollahi, M. M., Hamzehlou, S., Mehdipour, A. & Samadikuchaksaraei, A. Recombinant proteins: hopes for tissue engineering. BioImpacts 2, 123–125 (2012).
pubmed: 23678450
pmcid: 3648934
Esser, T. U., Trossmann, V. T., Lentz, S., Engel, F. B. & Scheibel, T. Designing of spider silk proteins for human induced pluripotent stem cell-based cardiac tissue engineering. Mater. Today Bio. 11, 100114 (2021).
pubmed: 34169268
pmcid: 8209670
doi: 10.1016/j.mtbio.2021.100114
Stoppel, W. L. et al. Elastic, silk-cardiac extracellular matrix hydrogels exhibit time-dependent stiffening that modulates cardiac fibroblast response. J. Biomed. Mater. Res. A 104, 3058–3072 (2016).
pubmed: 27480328
pmcid: 5805141
doi: 10.1002/jbm.a.35850
Hasturk, O., Jordan, K. E., Choi, J. & Kaplan, D. L. Enzymatically crosslinked silk and silk-gelatin hydrogels with tunable gelation kinetics, mechanical properties and bioactivity for cell culture and encapsulation. Biomaterials 232, 119720 (2020).
pubmed: 31896515
doi: 10.1016/j.biomaterials.2019.119720
Yildirim, Y. et al. Development of a biological ventricular assist device. Circulation 116, I-16–I-23 (2007).
doi: 10.1161/CIRCULATIONAHA.106.679688
Arai, K. et al. Fabrication of scaffold-free tubular cardiac constructs using a Bio-3D printer. PLoS ONE 13, e0209162 (2018).
pubmed: 30557409
pmcid: 6296519
doi: 10.1371/journal.pone.0209162
Tsuruyama, S., Matsuura, K., Sakaguchi, K. & Shimizu, T. Pulsatile tubular cardiac tissues fabricated by wrapping human iPS cells-derived cardiomyocyte sheets. Regen. Ther. 11, 297–305 (2019).
pubmed: 31667209
pmcid: 6813561
doi: 10.1016/j.reth.2019.09.001
Lee, A. et al. 3D bioprinting of collagen to rebuild components of the human heart. Science 365, 482–487 (2019).
pubmed: 31371612
doi: 10.1126/science.aav9051
Noor, N. et al. 3D printing of personalized thick and perfusable cardiac patches and hearts. Adv. Sci. 6, 1900344 (2019).
doi: 10.1002/advs.201900344
Ivey, M. J. & Tallquist, M. D. Defining the cardiac fibroblast: a new hope. Circ. J. 80, 2269–2276 (2016).
pubmed: 27746422
pmcid: 5588900
doi: 10.1253/circj.CJ-16-1003
Camelliti, P., Borg, T. K. & Kohl, P. Structural and functional characterisation of cardiac fibroblasts. Cardiovasc. Res. 65, 40–51 (2005).
pubmed: 15621032
doi: 10.1016/j.cardiores.2004.08.020
Talman, V. & Kivelä, R. Cardiomyocyte–endothelial cell interactions in cardiac remodeling and regeneration. Front. Cardiovasc. Med. 5, 101 (2018).
pubmed: 30175102
pmcid: 6108380
doi: 10.3389/fcvm.2018.00101
Colliva, A., Braga, L., Giacca, M. & Zacchigna, S. Endothelial cell–cardiomyocyte crosstalk in heart development and disease. J. Physiol. 598, 2923–2939 (2020).
pubmed: 30816576
doi: 10.1113/JP276758
Caspi, O. et al. Tissue engineering of vascularized cardiac muscle from human embryonic stem cells. Circ. Res. 100, 263–272 (2007).
pubmed: 17218605
doi: 10.1161/01.RES.0000257776.05673.ff
Tulloch, N. L. et al. Growth of engineered human myocardium with mechanical loading and vascular coculture. Circ. Res. 109, 47–59 (2011).
pubmed: 21597009
pmcid: 3140796
doi: 10.1161/CIRCRESAHA.110.237206
Nunes, S. S. et al. Biowire: a platform for maturation of human pluripotent stem cell–derived cardiomyocytes. Nat. Methods 10, 781–787 (2013).
pubmed: 23793239
pmcid: 4071061
doi: 10.1038/nmeth.2524
Ronaldson-Bouchard, K. et al. Advanced maturation of human cardiac tissue grown from pluripotent stem cells. Nature 556, 239–243 (2018).
pubmed: 29618819
pmcid: 5895513
doi: 10.1038/s41586-018-0016-3
Giacomelli, E. et al. Human-iPSC-derived cardiac stromal cells enhance maturation in 3d cardiac microtissues and reveal non-cardiomyocyte contributions to heart disease. Cell Stem Cell 26, 862–879.e11 (2020).
pubmed: 32459996
pmcid: 7284308
doi: 10.1016/j.stem.2020.05.004
Masumoto, H. et al. The myocardial regenerative potential of three-dimensional engineered cardiac tissues composed of multiple human iPS cell-derived cardiovascular cell lineages. Sci. Rep. 6, 29933 (2016).
pubmed: 27435115
pmcid: 4951692
doi: 10.1038/srep29933
Campostrini, G. et al. Generation, functional analysis and applications of isogenic three-dimensional self-aggregating cardiac microtissues from human pluripotent stem cells. Nat. Protoc. 16, 2213–2256 (2021).
pubmed: 33772245
pmcid: 7611409
doi: 10.1038/s41596-021-00497-2
Kamakura, T. et al. Ultrastructural maturation of human-induced pluripotent stem cell-derived cardiomyocytes in a long-term culture. Circ. J. 77, 1307–1314 (2013).
pubmed: 23400258
doi: 10.1253/circj.CJ-12-0987
Lundy, S. D., Zhu, W.-Z., Regnier, M. & Laflamme, M. A. Structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells. Stem. Cells Dev. 22, 1991–2002 (2013).
pubmed: 23461462
pmcid: 3699903
doi: 10.1089/scd.2012.0490
Mihic, A. et al. The effect of cyclic stretch on maturation and 3D tissue formation of human embryonic stem cell-derived cardiomyocytes. Biomaterials 35, 2798–2808 (2014).
pubmed: 24424206
doi: 10.1016/j.biomaterials.2013.12.052
Shadrin, I. Y. et al. Cardiopatch platform enables maturation and scale-up of human pluripotent stem cell-derived engineered heart tissues. Nat. Commun. 8, 1825 (2017).
pubmed: 29184059
pmcid: 5705709
doi: 10.1038/s41467-017-01946-x
Leonard, A. et al. Afterload promotes maturation of human induced pluripotent stem cell derived cardiomyocytes in engineered heart tissues. J. Mol. Cell. Cardiol. 118, 147–158 (2018).
pubmed: 29604261
pmcid: 5940558
doi: 10.1016/j.yjmcc.2018.03.016
Yang, X. et al. Tri-iodo-l-thyronine promotes the maturation of human cardiomyocytes-derived from induced pluripotent stem cells. J. Mol. Cell. Cardiol. 72, 296–304 (2014).
pubmed: 24735830
pmcid: 4041732
doi: 10.1016/j.yjmcc.2014.04.005
Parikh, S. S. et al. Thyroid and glucocorticoid hormones promote functional T-tubule development in human-induced pluripotent stem cell-derived cardiomyocytes. Circ. Res. 121, 1323–1330 (2017).
pubmed: 28974554
pmcid: 5722667
doi: 10.1161/CIRCRESAHA.117.311920
Lin, B. et al. Culture in glucose-depleted medium supplemented with fatty acid and 3,3’,5-triiodo-l-thyronine facilitates purification and maturation of human pluripotent stem cell-derived cardiomyocytes. Front. Endocrinol. 8, 253 (2017).
doi: 10.3389/fendo.2017.00253
Yang, X. et al. Fatty acids enhance the maturation of cardiomyocytes derived from human pluripotent stem cells. Stem Cell Rep. 13, 657–668 (2019).
doi: 10.1016/j.stemcr.2019.08.013
Horikoshi, Y. et al. Fatty acid-treated induced pluripotent stem cell-derived human cardiomyocytes exhibit adult cardiomyocyte-like energy metabolism phenotypes. Cells 8, 1095 (2019).
pmcid: 6769886
doi: 10.3390/cells8091095
Correia, C. et al. Distinct carbon sources affect structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells. Sci. Rep. 7, 8590 (2017).
pubmed: 28819274
pmcid: 5561128
doi: 10.1038/s41598-017-08713-4
Feyen, D. A. M. et al. Metabolic maturation media improve physiological function of human iPSC-derived cardiomyocytes. Cell Rep. 32, 107925 (2020).
pubmed: 32697997
doi: 10.1016/j.celrep.2020.107925
Chong, J. J. H. et al. Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature 510, 273–277 (2014).
pubmed: 24776797
pmcid: 4154594
doi: 10.1038/nature13233
Komae, H. et al. Three-dimensional functional human myocardial tissues fabricated from induced pluripotent stem cells. J. Tissue Eng. Regen. Med. 11, 926–935 (2017).
pubmed: 25628251
doi: 10.1002/term.1995
Seta, H., Matsuura, K., Sekine, H., Yamazaki, K. & Shimizu, T. Tubular cardiac tissues derived from human induced pluripotent stem cells generate pulse pressure in vivo. Sci. Rep. 7, 45499 (2017).
pubmed: 28358136
pmcid: 5371992
doi: 10.1038/srep45499
Goldsmith, E. C. et al. Organization of fibroblasts in the heart. Dev. Dyn. 230, 787–794 (2004).
pubmed: 15254913
doi: 10.1002/dvdy.20095
Rossi, G. et al. Capturing cardiogenesis in gastruloids. Cell Stem Cell 28, 230–240.e6 (2021).
pubmed: 33176168
doi: 10.1016/j.stem.2020.10.013
Drakhlis, L. et al. Human heart-forming organoids recapitulate early heart and foregut development. Nat. Biotechnol. 39, 737–746 (2021).
pubmed: 33558697
pmcid: 8192303
doi: 10.1038/s41587-021-00815-9
Hofbauer, P. et al. Cardioids reveal self-organizing principles of human cardiogenesis. Cell 184, 3299–3317.e22 (2021).
pubmed: 34019794
doi: 10.1016/j.cell.2021.04.034
Lee, B. W. et al. Modular assembly approach to engineer geometrically precise cardiovascular tissue. Adv. Healthc. Mater. 5, 900–906 (2016).
pubmed: 26865105
pmcid: 4836958
doi: 10.1002/adhm.201500956
Zhang, B. et al. Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis. Nat. Mater. 15, 669–678 (2016).
pubmed: 26950595
pmcid: 4879054
doi: 10.1038/nmat4570
Lai, B. F. L. et al. InVADE: integrated vasculature for assessing dynamic events. Adv. Funct. Mater. 27, 1703524 (2017).
doi: 10.1002/adfm.201703524
Zhang, Y. S. et al. Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip. Biomaterials 110, 45–59 (2016).
pubmed: 27710832
pmcid: 5198581
doi: 10.1016/j.biomaterials.2016.09.003
Skylar-Scott, M. A. et al. Biomanufacturing of organ-specific tissues with high cellular density and embedded vascular channels. Sci. Adv. 5, eaaw2459 (2019).
pubmed: 31523707
pmcid: 6731072
doi: 10.1126/sciadv.aaw2459
Ruskowitz, E. R. & DeForest, C. A. Photoresponsive biomaterials for targeted drug delivery and 4D cell culture. Nat. Rev. Mater. 3, 17087 (2018).
doi: 10.1038/natrevmats.2017.87
Brown, T. E. & Anseth, K. S. Spatiotemporal hydrogel biomaterials for regenerative medicine. Chem. Soc. Rev. 46, 6532–6552 (2017).
pubmed: 28820527
pmcid: 5662487
doi: 10.1039/C7CS00445A
DeForest, C. A., Polizzotti, B. D. & Anseth, K. S. Sequential click reactions for synthesizing and patterning three-dimensional cell microenvironments. Nat. Mater. 8, 659–664 (2009).
pubmed: 19543279
pmcid: 2715445
doi: 10.1038/nmat2473
Shadish, J. A., Benuska, G. M. & DeForest, C. A. Bioactive site-specifically modified proteins for 4D patterning of gel biomaterials. Nat. Mater. 18, 1005–1014 (2019).
pubmed: 31110347
pmcid: 6706293
doi: 10.1038/s41563-019-0367-7
Wang, G. et al. Modeling the mitochondrial cardiomyopathy of Barth syndrome with induced pluripotent stem cell and heart-on-chip technologies. Nat. Med. 20, 616–623 (2014).
pubmed: 24813252
pmcid: 4172922
doi: 10.1038/nm.3545
Hinson, J. T. et al. Titin mutations in iPS cells define sarcomere insufficiency as a cause of dilated cardiomyopathy. Science 349, 982–986 (2015).
pubmed: 26315439
pmcid: 4618316
doi: 10.1126/science.aaa5458
Mosqueira, D. et al. CRISPR/Cas9 editing in human pluripotent stem cell-cardiomyocytes highlights arrhythmias, hypocontractility, and energy depletion as potential therapeutic targets for hypertrophic cardiomyopathy. Eur. Heart J. 39, 3879–3892 (2018).
pubmed: 29741611
pmcid: 6234851
doi: 10.1093/eurheartj/ehy249
Mandegar, M. A. et al. CRISPR interference efficiently induces specific and reversible gene silencing in human iPSCs. Cell Stem Cell 18, 541–553 (2016).
pubmed: 26971820
pmcid: 4830697
doi: 10.1016/j.stem.2016.01.022
Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G. & Deisseroth, K. Millisecond-timescale, genetically targeted optical control of neural activity. Nat. Neurosci. 8, 1263–1268 (2005).
pubmed: 16116447
doi: 10.1038/nn1525
Dwenger, M. et al. Chronic optical pacing conditioning of h-iPSC engineered cardiac tissues. J. Tissue Eng. 10, 2041731419841748 (2019).
pubmed: 31024681
pmcid: 6472158
doi: 10.1177/2041731419841748
Dempsey, G. T. et al. Cardiotoxicity screening with simultaneous optogenetic pacing, voltage imaging and calcium imaging. J. Pharmacol. Toxicol. Methods 81, 240–250 (2016).
pubmed: 27184445
doi: 10.1016/j.vascn.2016.05.003
Klimas, A. et al. OptoDyCE as an automated system for high-throughput all-optical dynamic cardiac electrophysiology. Nat. Commun. 7, 11542 (2016).
pubmed: 27161419
pmcid: 4866323
doi: 10.1038/ncomms11542
Lemme, M. et al. Chronic intermittent tachypacing by an optogenetic approach induces arrhythmia vulnerability in human engineered heart tissue. Cardiovasc. Res. 116, 1487–1499 (2020).
pubmed: 31598634
doi: 10.1093/cvr/cvz245
Kwon, E. & Heo, W. D. Optogenetic tools for dissecting complex intracellular signaling pathways. Biochem. Biophys. Res. Commun. 527, 331–336 (2020).
pubmed: 31948753
doi: 10.1016/j.bbrc.2019.12.132
Park, H. et al. Optogenetic protein clustering through fluorescent protein tagging and extension of CRY2. Nat. Commun. 8, 30 (2017).
pubmed: 28646204
pmcid: 5482817
doi: 10.1038/s41467-017-00060-2
Kim, N. Y. et al. Optogenetic control of mRNA localization and translation in live cells. Nat. Cell Biol. 22, 341–352 (2020).
pubmed: 32066905
doi: 10.1038/s41556-020-0468-1
Ma, G. et al. Optogenetic engineering to probe the molecular choreography of STIM1-mediated cell signaling. Nat. Commun. 11, 1039 (2020).
pubmed: 32098964
pmcid: 7042325
doi: 10.1038/s41467-020-14841-9
Wearn, J. T., Technical Assistance of Zschiesche L. J. The extent of the capillary bed of the heart. J. Exp. Med. 47, 273–290 (1928).
pubmed: 19869413
pmcid: 2131359
doi: 10.1084/jem.47.2.273
Gordan, R., Gwathmey, J. K. & Xie, L.-H. Autonomic and endocrine control of cardiovascular function. World J. Cardiol. 7, 204–214 (2015).
pubmed: 25914789
pmcid: 4404375
doi: 10.4330/wjc.v7.i4.204
Oh, Y. et al. Functional coupling with cardiac muscle promotes maturation of hPSC-derived sympathetic neurons. Cell Stem Cell 19, 95–106 (2016).
pubmed: 27320040
pmcid: 4996639
doi: 10.1016/j.stem.2016.05.002
Winbo, A. et al. Functional coculture of sympathetic neurons and cardiomyocytes derived from human-induced pluripotent stem cells. Am. J. Physiol. Heart Circ. Physiol. 319, H927–H937 (2020).
pubmed: 32822546
doi: 10.1152/ajpheart.00546.2020
Takayama, Y. et al. Selective induction of human autonomic neurons enables precise control of cardiomyocyte beating. Sci. Rep. 10, 9464 (2020).
pubmed: 32528170
pmcid: 7289887
doi: 10.1038/s41598-020-66303-3
Dollinger, C. et al. Incorporation of resident macrophages in engineered tissues: multiple cell type response to microenvironment controlled macrophage-laden gelatine hydrogels. J. Tissue Eng. Regen. Med. 12, 330–340 (2018).
pubmed: 28482136
doi: 10.1002/term.2458
Lyadova, I., Gerasimova, T. & Nenasheva, T. Macrophages derived from human induced pluripotent stem cells: the diversity of protocols, future prospects, and outstanding questions. Front. Cell Dev. Biol. 9, 924 (2021).
doi: 10.3389/fcell.2021.640703
Mills, R. J. et al. Drug screening in human PSC-cardiac organoids identifies pro-proliferative compounds acting via the mevalonate pathway. Cell Stem Cell 24, 895–907.e6 (2019).
pubmed: 30930147
doi: 10.1016/j.stem.2019.03.009
Richards, D. J. et al. Human cardiac organoids for the modelling of myocardial infarction and drug cardiotoxicity. Nat. Biomed. Eng. 4, 446–462 (2020).
pubmed: 32284552
pmcid: 7422941
doi: 10.1038/s41551-020-0539-4
Rhee, J.-W. et al. Modeling secondary iron overload cardiomyopathy with human induced pluripotent stem cell-derived cardiomyocytes. Cell Rep. 32, 107886 (2020).
pubmed: 32668256
pmcid: 7553857
doi: 10.1016/j.celrep.2020.107886
Zhang, B. et al. Microfabrication of AngioChip, a biodegradable polymer scaffold with microfluidic vasculature. Nat. Protoc. 13, 1793–1813 (2018).
pubmed: 30072724
doi: 10.1038/s41596-018-0015-8
Help Therapeutics. Epicardial Injection of Allogeneic Human Pluripotent Stem Cell-derived Cardiomyocytes to Treat Severe Chronic Heart Failure https://clinicaltrials.gov/ct2/show/NCT03763136 (2021).
Gavenis, K. Safety and Efficacy of Induced Pluripotent Stem Cell-derived Engineered Human Myocardium as Biological Ventricular Assist Tissue in Terminal Heart Failure https://clinicaltrials.gov/ct2/show/NCT04396899 (2021).
Huebsch, N. et al. Automated video-based analysis of contractility and calcium flux in human-induced pluripotent stem cell-derived cardiomyocytes cultured over different spatial scales. Tissue Eng. Part C Methods 21, 467–479 (2015).
pubmed: 25333967
pmcid: 4410286
doi: 10.1089/ten.tec.2014.0283
Sharma, A., Toepfer, C. N., Schmid, M., Garfinkel, A. C. & Seidman, C. E. Differentiation and contractile analysis of GFP-sarcomere reporter hiPSC-cardiomyocytes. Curr. Protoc. Hum. Genet. 96, 21.12.1–21.12.12 (2018).
Toepfer, C. N. et al. SarcTrack. Circ. Res. 124, 1172–1183 (2019).
pubmed: 30700234
pmcid: 6485312
doi: 10.1161/CIRCRESAHA.118.314505
Psaras, Y. et al. CalTrack: high-throughput automated calcium transient analysis in cardiomyocytes. Circ. Res. 129, 326–341 (2021).
pubmed: 34018815
pmcid: 8260473
doi: 10.1161/CIRCRESAHA.121.318868
Bock, C., Farlik, M. & Sheffield, N. C. Multi-omics of single cells: strategies and applications. Trends Biotechnol. 34, 605–608 (2016).
pubmed: 27212022
pmcid: 4959511
doi: 10.1016/j.tibtech.2016.04.004
Manzoni, C. et al. Genome, transcriptome and proteome: the rise of omics data and their integration in biomedical sciences. Brief. Bioinform. 19, 286–302 (2018).
pubmed: 27881428
doi: 10.1093/bib/bbw114
Bai, D., Peng, J. & Yi, C. Advances in single-cell multi-omics profiling. RSC Chem. Biol. 2, 441–449 (2021).
pubmed: 34458793
pmcid: 8341011
doi: 10.1039/D0CB00163E
Asp, M. et al. A spatiotemporal organ-wide gene expression and cell atlas of the developing human heart. Cell 179, 1647–1660.e19 (2019).
pubmed: 31835037
doi: 10.1016/j.cell.2019.11.025
Litviňuková, M. et al. Cells of the adult human heart. Nature 588, 466–472 (2020).
pubmed: 32971526
pmcid: 7681775
doi: 10.1038/s41586-020-2797-4
Yechikov, S. et al. NODAL inhibition promotes differentiation of pacemaker-like cardiomyocytes from human induced pluripotent stem cells. Stem Cell Res. 49, 102043 (2020).
pubmed: 33128951
pmcid: 7814970
doi: 10.1016/j.scr.2020.102043
Devalla, H. D. et al. Atrial-like cardiomyocytes from human pluripotent stem cells are a robust preclinical model for assessing atrial-selective pharmacology. EMBO Mol. Med. 7, 394–410 (2015).
pubmed: 25700171
pmcid: 4403042
doi: 10.15252/emmm.201404757
Guadix, J. A. et al. Human pluripotent stem cell differentiation into functional epicardial progenitor cells. Stem Cell Rep. 9, 1754–1764 (2017).
doi: 10.1016/j.stemcr.2017.10.023
Yao, S. et al. Long-term self-renewal and directed differentiation of human embryonic stem cells in chemically defined conditions. Proc. Natl Acad. Sci. USA 103, 6907–6912 (2006).
pubmed: 16632596
pmcid: 1458992
doi: 10.1073/pnas.0602280103
Takei, S. et al. Bone morphogenetic protein-4 promotes induction of cardiomyocytes from human embryonic stem cells in serum-based embryoid body development. Am. J. Physiol. Heart Circ. Physiol. 296, H1793–H1803 (2009).
pubmed: 19363129
doi: 10.1152/ajpheart.01288.2008
Li, J. et al. Human pluripotent stem cell-derived cardiac tissue-like constructs for repairing the infarcted myocardium. Stem Cell Rep. 9, 1546–1559 (2017).
doi: 10.1016/j.stemcr.2017.09.007
Han, J., Wu, Q., Xia, Y., Wagner, M. B. & Xu, C. Cell alignment induced by anisotropic electrospun fibrous scaffolds alone has limited effect on cardiomyocyte maturation. Stem Cell Res. 16, 740–750 (2016).
pubmed: 27131761
pmcid: 4903921
doi: 10.1016/j.scr.2016.04.014
Kaiser, N. J., Kant, R. J., Minor, A. J. & Coulombe, K. L. K. Optimizing blended collagen-fibrin hydrogels for cardiac tissue engineering with human iPSC-derived cardiomyocytes. ACS Biomater. Sci. Eng. 5, 887–899 (2019).
pubmed: 30775432
doi: 10.1021/acsbiomaterials.8b01112
Rogers, A. J., Fast, V. G. & Sethu, P. Biomimetic cardiac tissue model enables the adaption of human induced pluripotent stem cell cardiomyocytes to physiological hemodynamic loads. Anal. Chem. 88, 9862–9868 (2016).
pubmed: 27620367
pmcid: 6050012
doi: 10.1021/acs.analchem.6b03105
Ruan, J.-L. et al. Mechanical stress promotes maturation of human myocardium from pluripotent stem cell-derived progenitors. Stem Cells 33, 2148–2157 (2015).
pubmed: 25865043
pmcid: 4478130
doi: 10.1002/stem.2036
Ulmer, B. M. et al. Contractile work contributes to maturation of energy metabolism in hiPSC-derived cardiomyocytes. Stem Cell Rep. 10, 834–847 (2018).
doi: 10.1016/j.stemcr.2018.01.039
Ruan, J.-L. et al. Mechanical stress conditioning and electrical stimulation promote contractility and force maturation of induced pluripotent stem cell-derived human cardiac tissue. Circulation 134, 1557–1567 (2016).
pubmed: 27737958
pmcid: 5123912
doi: 10.1161/CIRCULATIONAHA.114.014998
Marchianò, S., Bertero, A. & Murry, C. E. Learn from your elders: developmental biology lessons to guide maturation of stem cell-derived cardiomyocytes. Pediatr. Cardiol. 40, 1367–1387 (2019).
pubmed: 31388700
pmcid: 6786957
doi: 10.1007/s00246-019-02165-5
Wiegerinck, R. F. et al. Force frequency relationship of the human ventricle increases during early postnatal development. Pediatr. Res. 65, 414–419 (2009).
pubmed: 19127223
pmcid: 2788428
doi: 10.1203/PDR.0b013e318199093c
Yang, X., Pabon, L. & Murry, C. E. Engineering adolescence. Circ. Res. 114, 511–523 (2014).
pubmed: 24481842
pmcid: 3955370
doi: 10.1161/CIRCRESAHA.114.300558
Feric, N. T. & Radisic, M. Maturing human pluripotent stem cell-derived cardiomyocytes in human engineered cardiac tissues. Adv. Drug Deliv. Rev. 96, 110–134 (2016).
pubmed: 25956564
doi: 10.1016/j.addr.2015.04.019
Lopaschuk, G. D. & Jaswal, J. S. Energy metabolic phenotype of the cardiomyocyte during development, differentiation, and postnatal. J. Cardiovasc. Pharmacol. 56, 130–140 (2010).
pubmed: 20505524
doi: 10.1097/FJC.0b013e3181e74a14