Fabrication of heart tubes from iPSC derived cardiomyocytes and human fibrinogen by rotating mold technology.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
07 Jun 2024
07 Jun 2024
Historique:
received:
06
03
2024
accepted:
04
06
2024
medline:
8
6
2024
pubmed:
8
6
2024
entrez:
7
6
2024
Statut:
epublish
Résumé
Due to its structural and functional complexity the heart imposes immense physical, physiological and electromechanical challenges on the engineering of a biological replacement. Therefore, to come closer to clinical translation, the development of a simpler biological assist device is requested. Here, we demonstrate the fabrication of tubular cardiac constructs with substantial dimensions of 6 cm in length and 11 mm in diameter by combining human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and human foreskin fibroblast (hFFs) in human fibrin employing a rotating mold technology. By centrifugal forces employed in the process a cell-dense layer was generated enabling a timely functional coupling of iPSC-CMs demonstrated by a transgenic calcium sensor, rhythmic tissue contractions, and responsiveness to electrical pacing. Adjusting the degree of remodeling as a function of hFF-content and inhibition of fibrinolysis resulted in stable tissue integrity for up to 5 weeks. The rotating mold device developed in frame of this work enabled the production of tubes with clinically relevant dimensions of up to 10 cm in length and 22 mm in diameter which-in combination with advanced bioreactor technology for controlled production of functional iPSC-derivatives-paves the way towards the clinical translation of a biological cardiac assist device.
Identifiants
pubmed: 38849457
doi: 10.1038/s41598-024-64022-7
pii: 10.1038/s41598-024-64022-7
doi:
Substances chimiques
Fibrinogen
9001-32-5
Fibrin
9001-31-4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
13174Informations de copyright
© 2024. The Author(s).
Références
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. https://doi.org/10.1038/s41467-017-01946-x (2017).
doi: 10.1038/s41467-017-01946-x
pubmed: 29184059
pmcid: 5705709
Tiburcy, M. et al. Defined engineered human myocardium with advanced maturation for applications in heart failure modeling and repair. Circulation 135, 1832–1847. https://doi.org/10.1161/CIRCULATIONAHA.116.024145 (2017).
doi: 10.1161/CIRCULATIONAHA.116.024145
pubmed: 28167635
pmcid: 5501412
Jackman, C. P., Carlson, A. L. & Bursac, N. Dynamic culture yields engineered myocardium with near-adult functional output. Biomaterials 111, 66–79. https://doi.org/10.1016/j.biomaterials.2016.09.024 (2016).
doi: 10.1016/j.biomaterials.2016.09.024
pubmed: 27723557
pmcid: 5074846
Miyagawa, S. et al. Case report: Transplantation of human induced pluripotent stem cell-derived cardiomyocyte patches for ischemic cardiomyopathy. Front. Cardiovasc. Med. 9, 950829. https://doi.org/10.3389/fcvm.2022.950829 (2022).
doi: 10.3389/fcvm.2022.950829
pubmed: 36051285
pmcid: 9426776
Kawamura, T. et al. Safety confirmation of induced pluripotent stem cell-derived cardiomyocyte patch transplantation for ischemic cardiomyopathy: First three case reports. Front. Cardiovasc. Med. 10, 1182209. https://doi.org/10.3389/fcvm.2023.1182209 (2023).
doi: 10.3389/fcvm.2023.1182209
pubmed: 37781295
pmcid: 10540447
Sridharan, D. et al. Preclinical large animal porcine models for cardiac regeneration and its clinical translation: Role of hiPSC-derived cardiomyocytes. Cells. https://doi.org/10.3390/cells12071090 (2023).
doi: 10.3390/cells12071090
pubmed: 37048163
pmcid: 10093073
Kishino, Y. et al. Cardiac regenerative therapy using human pluripotent stem cells for heart failure: A state-of-the-art review. J. Card. Fail 29, 503–513. https://doi.org/10.1016/j.cardfail.2022.10.433 (2023).
doi: 10.1016/j.cardfail.2022.10.433
pubmed: 37059512
MacQueen, L. A. et al. A tissue-engineered scale model of the heart ventricle. Nat. Biomed. Eng. 2, 930–941. https://doi.org/10.1038/s41551-018-0271-5 (2018).
doi: 10.1038/s41551-018-0271-5
pubmed: 31015723
pmcid: 6774355
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. https://doi.org/10.1016/j.reth.2019.09.001 (2019).
doi: 10.1016/j.reth.2019.09.001
pubmed: 31667209
pmcid: 6813561
Park, J. et al. Modular design of a tissue engineered pulsatile conduit using human induced pluripotent stem cell-derived cardiomyocytes. Acta Biomater. 102, 220–230. https://doi.org/10.1016/j.actbio.2019.10.019 (2020).
doi: 10.1016/j.actbio.2019.10.019
pubmed: 31634626
Williams, N. P. et al. Engineering anisotropic 3D tubular tissues with flexible thermoresponsive nanofabricated substrates. Biomaterials 240, 119856. https://doi.org/10.1016/j.biomaterials.2020.119856 (2020).
doi: 10.1016/j.biomaterials.2020.119856
pubmed: 32105818
pmcid: 7536133
Kohne, M. et al. A potential future Fontan modification: Preliminary in vitro data of a pressure-generating tube from engineered heart tissue. Eur. J. Cardiothorac. Surg. https://doi.org/10.1093/ejcts/ezac111 (2022).
doi: 10.1093/ejcts/ezac111
pubmed: 35218664
pmcid: 9373941
Bliley, J. et al. FRESH 3D bioprinting a contractile heart tube using human stem cell-derived cardiomyocytes. Biofabrication https://doi.org/10.1088/1758-5090/ac58be (2022).
doi: 10.1088/1758-5090/ac58be
pubmed: 35213846
pmcid: 9206822
Guyette, J. P. et al. Bioengineering human myocardium on native extracellular matrix. Circ. Res. 118, 56–72. https://doi.org/10.1161/CIRCRESAHA.115.306874 (2016).
doi: 10.1161/CIRCRESAHA.115.306874
pubmed: 26503464
Noor, N. et al. 3D printing of personalized thick and perfusable cardiac patches and hearts. Adv. Sci. (Weinh) 6, 1900344. https://doi.org/10.1002/advs.201900344 (2019).
doi: 10.1002/advs.201900344
pubmed: 31179230
pmcid: 6548966
Kupfer, M. E. et al. In situ expansion, differentiation and electromechanical coupling of human cardiac muscle in a 3D bioprinted, chambered organoid. Circ. Res. https://doi.org/10.1161/CIRCRESAHA.119.316155 (2020).
doi: 10.1161/CIRCRESAHA.119.316155
pubmed: 32228120
pmcid: 8210857
Kensah, G. et al. Murine and human pluripotent stem cell-derived cardiac bodies form contractile myocardial tissue in vitro. Eur. Heart J. 34, 1134–1146. https://doi.org/10.1093/eurheartj/ehs349 (2013).
doi: 10.1093/eurheartj/ehs349
pubmed: 23103664
Ke, M. et al. Construction of millimeter-scale vascularized engineered myocardial tissue using a mixed gel. Regen. Biomater. 11, 0117. https://doi.org/10.1093/rb/rbad117 (2024).
doi: 10.1093/rb/rbad117
Goldfracht, I. et al. Engineered heart tissue models from hiPSC-derived cardiomyocytes and cardiac ECM for disease modeling and drug testing applications. Acta Biomater. 92, 145–159. https://doi.org/10.1016/j.actbio.2019.05.016 (2019).
doi: 10.1016/j.actbio.2019.05.016
pubmed: 31075518
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. https://doi.org/10.1021/acsbiomaterials.8b01112 (2019).
doi: 10.1021/acsbiomaterials.8b01112
pubmed: 30775432
Park, C. H. & Woo, K. M. Fibrin-based biomaterial applications in tissue engineering and regenerative medicine. Adv. Exp. Med. Biol. 1064, 253–261. https://doi.org/10.1007/978-981-13-0445-3_16 (2018).
doi: 10.1007/978-981-13-0445-3_16
pubmed: 30471038
Mannucci, P. M. Hemostatic drugs. N. Engl. J. Med. 339, 245–253. https://doi.org/10.1056/NEJM199807233390407 (1998).
doi: 10.1056/NEJM199807233390407
pubmed: 9673304
Aper, T. et al. Novel method for the generation of tissue-engineered vascular grafts based on a highly compacted fibrin matrix. Acta Biomater. 29, 21–32. https://doi.org/10.1016/j.actbio.2015.10.012 (2016).
doi: 10.1016/j.actbio.2015.10.012
pubmed: 26472610
Regenberg, M. C., Wilhelmi, M., Hilfiker, A., Haverich, A. & Aper, T. Development, comparative structural analysis, and first in vivo evaluation of acellular implanted highly compacted fibrin tubes for arterial bypass grafting. J. Mech. Behav. Biomed. Mater. 148, 106199. https://doi.org/10.1016/j.jmbbm.2023.106199 (2023).
doi: 10.1016/j.jmbbm.2023.106199
pubmed: 37922760
Haase, A. et al. Establishment of MHHi001-A-5, a GCaMP6f and RedStar dual reporter human iPSC line for in vitro and in vivo characterization and in situ tracing of iPSC derivatives. Stem Cell Res. 52, 102206. https://doi.org/10.1016/j.scr.2021.102206 (2021).
doi: 10.1016/j.scr.2021.102206
pubmed: 33571874
Halloin, C. et al. Continuous WNT control enables advanced hPSC cardiac processing and prognostic surface marker identification in chemically defined suspension culture. Stem Cell Rep. 13, 366–379. https://doi.org/10.1016/j.stemcr.2019.06.004 (2019).
doi: 10.1016/j.stemcr.2019.06.004
Kriedemann, N. T. W. et al. Standardized production of hPSC-derived cardiomyocyte aggregates in stirred spinner flasks. Nat. Protoc. https://doi.org/10.1038/s41596-024-00976-2 (2024).
doi: 10.1038/s41596-024-00976-2
pubmed: 38548938
Andree, B. et al. Formation of three-dimensional tubular endothelial cell networks under defined serum-free cell culture conditions in human collagen hydrogels. Sci. Rep. 9, 5437. https://doi.org/10.1038/s41598-019-41985-6 (2019).
doi: 10.1038/s41598-019-41985-6
pubmed: 30932006
pmcid: 6443732
Haase, A., Gohring, G. & Martin, U. Generation of non-transgenic iPS cells from human cord blood CD34(+) cells under animal component-free conditions. Stem Cell Res. 21, 71–73. https://doi.org/10.1016/j.scr.2017.03.022 (2017).
doi: 10.1016/j.scr.2017.03.022
pubmed: 28677540
Kensah, G. et al. A novel miniaturized multimodal bioreactor for continuous in situ assessment of bioartificial cardiac tissue during stimulation and maturation. Tissue Eng. C Methods 17, 463–473. https://doi.org/10.1089/ten.TEC.2010.0405 (2011).
doi: 10.1089/ten.TEC.2010.0405
Tirziu, D., Giordano, F. J. & Simons, M. Cell communications in the heart. Circulation 122, 928–937. https://doi.org/10.1161/CIRCULATIONAHA.108.847731 (2010).
doi: 10.1161/CIRCULATIONAHA.108.847731
pubmed: 20805439
pmcid: 2941440
Boucard, E. et al. The degradation of gelatin/alginate/fibrin hydrogels is cell type dependent and can be modulated by targeting fibrinolysis. Front. Bioeng. Biotechnol. 10, 920929. https://doi.org/10.3389/fbioe.2022.920929 (2022).
doi: 10.3389/fbioe.2022.920929
pubmed: 35935486
pmcid: 9355319
Syedain, Z. H., Meier, L. A., Bjork, J. W., Lee, A. & Tranquillo, R. T. Implantable arterial grafts from human fibroblasts and fibrin using a multi-graft pulsed flow-stretch bioreactor with noninvasive strength monitoring. Biomaterials 32, 714–722. https://doi.org/10.1016/j.biomaterials.2010.09.019 (2011).
doi: 10.1016/j.biomaterials.2010.09.019
pubmed: 20934214
Syedain, Z. H. et al. Pediatric tri-tube valved conduits made from fibroblast-produced extracellular matrix evaluated over 52 weeks in growing lambs. Sci. Transl. Med. https://doi.org/10.1126/scitranslmed.abb7225 (2021).
doi: 10.1126/scitranslmed.abb7225
pubmed: 33731437
Jung, S. A. et al. Fibrin-dextran hydrogels with tunable porosity and mechanical properties. Biomacromolecules 24, 3972–3984. https://doi.org/10.1021/acs.biomac.3c00269 (2023).
doi: 10.1021/acs.biomac.3c00269
pubmed: 37574715
Querdel, E. et al. Human engineered heart tissue patches remuscularize the injured heart in a dose-dependent manner. Circulation 143, 1991–2006. https://doi.org/10.1161/CIRCULATIONAHA.120.047904 (2021).
doi: 10.1161/CIRCULATIONAHA.120.047904
pubmed: 33648345
pmcid: 8126500
Chiu, L. L. Y. & Radisic, M. Cardiac tissue engineering. Curr. Opin. Chem. Eng. 2, 41–52. https://doi.org/10.1016/j.coche.2013.01.002 (2013).
doi: 10.1016/j.coche.2013.01.002
Avram, R. et al. Real-world heart rate norms in the Health eHeart study. NPJ. Digit. Med. 2, 58. https://doi.org/10.1038/s41746-019-0134-9 (2019).
doi: 10.1038/s41746-019-0134-9
pubmed: 31304404
pmcid: 6592896
Fleischer, S., Jahnke, H. G., Fritsche, E., Girard, M. & Robitzki, A. A. Comprehensive human stem cell differentiation in a 2D and 3D mode to cardiomyocytes for long-term cultivation and multiparametric monitoring on a multimodal microelectrode array setup. Biosens. Bioelectron. 126, 624–631. https://doi.org/10.1016/j.bios.2018.10.061 (2019).
doi: 10.1016/j.bios.2018.10.061
pubmed: 30508787
Ergir, E. et al. Generation and maturation of human iPSC-derived 3D organotypic cardiac microtissues in long-term culture. Sci. Rep. 12, 17409. https://doi.org/10.1038/s41598-022-22225-w (2022).
doi: 10.1038/s41598-022-22225-w
pubmed: 36257968
pmcid: 9579206
Gruh, I. et al. Cell therapy with human iPSC-derived cardiomyocyte aggregates leads to efficient engraftment and functional recovery after myocardial infarction in non-human primates. BioRxiv. https://doi.org/10.1101/2023.12.31.573775 (2024).
doi: 10.1101/2023.12.31.573775
Liu, Y. W. et al. Human embryonic stem cell-derived cardiomyocytes restore function in infarcted hearts of non-human primates. Nat. Biotechnol. 36, 597–605. https://doi.org/10.1038/nbt.4162 (2018).
doi: 10.1038/nbt.4162
pubmed: 29969440
pmcid: 6329375
Olmer, R. et al. Differentiation of human pluripotent stem cells into functional endothelial cells in scalable suspension culture. Stem Cell Rep. 10, 1657–1672. https://doi.org/10.1016/j.stemcr.2018.03.017 (2018).
doi: 10.1016/j.stemcr.2018.03.017
Grune, T., Ott, C., Haseli, S., Hohn, A. & Jung, T. The, “MYOCYTER”—Convert cellular and cardiac contractions into numbers with ImageJ. Sci. Rep. 9, 15112. https://doi.org/10.1038/s41598-019-51676-x (2019).
doi: 10.1038/s41598-019-51676-x
pubmed: 31641278
pmcid: 6805901