Scilight Press

Author Information

Received: 04 Apr 2024 | Revised: 29 May 2024 | Accepted: 29 May 2024 | Published: 29 Aug 2024

Abstract

Keywords

3D culture | cardiac organoids | self-assembling | drug-screening | disease modeling

References 

• 1.
  Virani, S.S.; Alonso, A.; Aparicio, H.J.; et al. Heart disease and stroke statistics-2021 update: A report from the American heart association. Circulation 2021, 143, e254–e743.
• 2.
  Lewis-Israeli, Y.R.; Wasserman, A.H.; Aguirre, A. Heart Organoids and Engineered Heart Tissues: Novel Tools for Modeling Human Cardiac Biology and Disease. Biomolecules 2021, 11, 1277.
• 3.
  Liu, C.; Feng, X.; Li, G.; et al. Generating 3D human cardiac constructs from pluripotent stem cells. EBioMedicine 2022, 76, 103813.
• 4.
  Peng, K.; Li, X.; Wu, C.; et al. Derivation of haploid trophoblast stem cells via conversion in vitro. iScience. 2019, 11, 508–518.
• 5.
  Sharma, P.; Gentile, C. Cardiac spheroids as in vitro bioengineered heart tissues to study human heart pathophysiology. J. Vis. Exp. 2021, 167, e61962.
• 6.
  Stiefbold, M.; Zhang, H.; Wan, L.Q. Engineered platforms for mimicking cardiac development and drug screening. Cell. Mol. Life Sci. 2024, 81, 197.
• 7.
  Drakhlis, L.; Biswanath, S.; Farr, C.M.; et al. Human heart-forming organoids recapitulate early heart and foregut development. Nat. Biotechnol. 2021, 39, 737–746.
• 8.
  Hofbauer, P.; Jahnel, S.M.; Papai, N.; et al. Cardioids reveal self-organizing principles of human cardiogenesis. Cell 2021, 184, 3299–3317.
• 9.
  Rossi, G.; Broguiere, N.; Miyamoto, M.; et al. Capturing Cardiogenesis in Gastruloids. Cell Stem Cell 2021, 28, 230–240.
• 10.
  Zimmermann, W.H.; Schneiderbanger, K.; Schubert, P.; et al. Tissue engineering of a differentiated cardiac muscle construct. Circ. Res. 2002, 90, 223–230.
• 11.
  Mills, R.J.; Titmarsh, D.M.; Koenig, X.; et al. Functional screening in human cardiac organoids reveals a metabolic mechanism for cardiomyocyte cell cycle arrest. Proc. Natl. Acad. Sci. USA 2017, 114, E8372–E8381.
• 12.
  Voges, H.K.; Mills, R.J.; Elliott, D.A.; et al. Development of a human cardiac organoid injury model reveals innate regenerative potential. Development 2017, 144, 1118–1127.
• 13.
  Chen, Y.; Feng, J.; Zhao, S.; et al. Long-Term Engraftment Promotes Differentiation of Alveolar Epithelial Cells from Human Embryonic Stem Cell Derived Lung Organoids. Stem Cells Dev. 2018, 27, 1339–1349.
• 14.
  Wang, X.; Yuan, Y.; Didelija, I.C.; et al. Ex Vivo Enteroids Recapitulate In Vivo Citrulline Production in Mice. J. Nutr. 2018, 148, 1415–1420.
• 15.
  Lai Benjamin, F.L.; Lu RickX.; Hu, Y.; et al. Recapitulating pancreatic tumor microenvironment through synergistic use of patient organoids and organ-on-a-chip vasculature. Adv. Funct. Mater. 2020, 30, 2000545.
• 16.
  Gomez-Mariano, G.; Matamala, N.; Martinez, S.; et al. Liver organoids reproduce alpha-1 antitrypsin deficiency-related liver disease. Hepatol. Int. 2020, 14, 127–137.
• 17.
  Gleave, A.M.; Ci, X.; Lin, D.; et al. A synopsis of prostate organoid methodologies, applications, and limitations. Prostate 2020, 80, 518–526.
• 18.
  Nowogrodzki, A. How cerebral organoids are guiding brain-cancer research and therapies. Nature 2018, 561, S48–S49.
• 19.
  Maru, Y.; Tanaka, N.; Itami, M.; et al. Efficient use of patient-derived organoids as a preclinical model for gynecologic tumors. Gynecol. Oncol. 2019, 154, 189–198.
• 20.
  Corro, C.; Novellasdemunt, L.; Li, V.S.W. A brief history of organoids. Am. J. Physiol. Cell Physiol. 2020, 319, C151–C165.
• 21.
  Schmidt, C.; Deyett, A.; Ilmer, T.; et al. Multi-chamber cardioids unravel human heart development and cardiac defects. Cell 2023, 186, 5587–5605.
• 22.
  Paik, D.T.; Cho, S.; Tian, L.; et al. Single-cell RNA sequencing in cardiovascular development, disease and medicine. Nat. Rev. Cardiol. 2020, 17, 457–473.
• 23.
  Paik, D.T.; Chandy, M.; Wu, J.C. Patient and Disease-Specific Induced Pluripotent Stem Cells for Discovery of Personalized Cardiovascular Drugs and Therapeutics. Pharmacol. Rev. 2020, 72, 320–342.
• 24.
  Tang, Y.; Nyengaard, J.R.; Andersen, J.B.; et al. The application of stereological methods for estimating structural parameters in the human heart. Anat. Rec. 2009, 292, 1630–1647.
• 25.
  Bergmann, O.; Zdunek, S.; Felker, A.; et al. Dynamics of Cell Generation and Turnover in the Human Heart. Cell 2015, 161, 1566–1575.
• 26.
  Pinto, A.R.; Ilinykh, A.; Ivey, M.J.; et al. Revisiting Cardiac Cellular Composition. Circ. Res. 2016, 118, 400–409.
• 27.
  Seguret, M.; Vermersch, E.; Jouve, C.; et al. Cardiac Organoids to Model and Heal Heart Failure and Cardiomyopathies. Biomedicines 2021, 9, 563.
• 28.
  Schwach, V.; Passier, R. Native cardiac environment and its impact on engineering cardiac tissue. Biomater. Sci. 2019, 7, 3566–3580.
• 29.
  Rossi, G.; Manfrin, A.; Lutolf, M.P. Progress and potential in organoid research. Nat. Rev. Genet. 2018, 19, 671–687.
• 30.
  Cashman, T.J.; Josowitz, R.; Johnson, B.V.; et al. Human Engineered Cardiac Tissues Created Using Induced Pluripotent Stem Cells Reveal Functional Characteristics of BRAF-Mediated Hypertrophic Cardiomyopathy. PLoS ONE 2016, 11, e0146697.
• 31.
  Hofbauer, P.; Jahnel, S.M.; Mendjan, S. In vitro models of the human heart. Development 2021, 148, dev199672.
• 32.
  Silva, A.C.; Matthys, O.B.; Joy, D.A.; et al. Co-emergence of cardiac and gut tissues promotes cardiomyocyte maturation within human iPSC-derived organoids. Cell Stem Cell 2021, 28, 2137–2152.
• 33.
  Little, M.H.; Combes, A.N. Kidney organoids: Accurate models or fortunate accidents. Genes Dev. 2019, 33, 1319–1345.
• 34.
  Ming, Y.; Hao, S.; Wang, F.; et al. Longitudinal morphological and functional characterization of human heart organoids using optical coherence tomography. Biosens. Bioelectron. 2022, 207, 114136.
• 35.
  Chen, G.; Ning, B.; Shi, T. Single-Cell RNA-Seq Technologies and Related Computational Data Analysis. Front. Genet. 2019, 10, 317.
• 36.
  Asp, M.; Giacomello, S.; Larsson, L.; et al. A Spatiotemporal Organ-Wide Gene Expression and Cell Atlas of the Developing Human Heart. Cell. 2019, 179, 1647–1660.
• 37.
  Gu, Y.; Gorelik, J.; Spohr, H.A.; et al. High-resolution scanning patch-clamp: New insights into cell function. FASEB J. 2002, 16, 748–750.
• 38.
  Yamamoto, Y.; Hirose, S.; Wuriyanghai, Y.; et al. Electrophysiological Analysis of hiPSC-Derived Cardiomyocytes Using a Patch-Clamp Technique. Methods Mol. Biol. 2021, 2320, 1211–1233.
• 39.
  Navarrete, E.G.; Liang, P.; Lan, F.; et al. Screening drug-induced arrhythmia using human induced pluripotent stem cell-derived cardiomyocytes and low-impedance microelectrode arrays. Circulation 2013, 128, S3–S13.
• 40.
  66.Muller, J.; Ballini, M.; Livi, P.; et al. High-resolution CMOS MEA platform to study neurons at subcellular, cellular, and network levels. Lab. Chip. 2015, 15, 2767–2780.
• 41.
  Eisner, D.A.; Caldwell, J.L.; Kistamas, K.; et al. Calcium and Excitation-Contraction Coupling in the Heart. Circ. Res. 2017, 121, 181–195.
• 42.
  Zhang, J.Z.; Zhao, S.R.; Tu, C.; et al. Protocol to measure contraction, calcium, and action potential in human-induced pluripotent stem cell-derived cardiomyocytes. STAR Protoc. 2021, 2, 100859.
• 43.
  Lee, J.; Sutani, A.; Kaneko, R.; et al. In vitro generation of functional murine heart organoids via FGF4 and extracellular matrix. Nat. Commun. 2020, 11, 4283.
• 44.
  Horikoshi, Y.; Yan, Y.; Terashvili, M.; et al. Fatty Acid-Treated Induced Pluripotent Stem Cell-Derived Human Cardiomyocytes Exhibit Adult Cardiomyocyte-Like Energy Metabolism Phenotypes. Cells 2019, 8, 1095.
• 45.
  Dorn G.W., 2nd. Mitochondrial dynamism and heart disease: Changing shape and shaping change. EMBO Mol. Med. 2015, 7, 865–877.
• 46.
  Kim, H.; Kamm, R.D.; Vunjak-Novakovic, G.; et al. Progress in multicellular human cardiac organoids for clinical applications. Cell Stem Cell. 2022, 29, 503–514.
• 47.
  Schermelleh, L.; Heintzmann, R.; Leonhardt, H. A guide to super-resolution fluorescence microscopy. J. Cell Biol. 2010, 190, 165.
• 48.
  Smith, C.L. Basic confocal microscopy. In Basic Confocal Microscopy; Springer: New York, NY, USA, 2001; Chapter 2, Unit 2.2.
• 49.
  Richards, D.J.; Li, Y.; Kerr, C.M.; et al. Human cardiac organoids for the modelling of myocardial infarction and drug cardiotoxicity. Nat. Biomed. Eng. 2020, 4, 446–462.
• 50.
  Ueda, H.R.; Erturk, A.; Chung, K.; et al. Tissue clearing and its applications in neuroscience. Nat. Rev. Neurosci. 2020, 21, 61–79.
• 51.
  Huebsch, N.; Loskill, P.; Mandegar, M.A.; 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 2015, 21, 467–479.
• 52.
  Hayes, H.B.; Nicolini, A.M.; Arrowood, C.A.; et al. Novel method for action potential measurements from intact cardiac monolayers with multiwell microelectrode array technology. Sci. Rep. 2019, 9, 11893.
• 53.
  Gao, J.; Liao, C.; Liu, S.; et al. Nanotechnology: New opportunities for the development of patch-clamps. J. Nanobiotechnology. 2021, 19, 97.
• 54.
  Passaro, A.P.; Stice, S.L. Electrophysiological Analysis of Brain Organoids: Current Approaches and Advancements. Front. Neurosci. 2020, 14, 622137.
• 55.
  Le Floch, P.; Li, Q.; Lin, Z.; et al. Stretchable Mesh Nanoelectronics for 3D Single-Cell Chronic Electrophysiology from Developing Brain Organoids. Adv. Mater. 2022, 34, e2106829.
• 56.
  Li, Q.; Nan, K.; Le Floch, P.; et al. Cyborg Organoids: Implantation of Nanoelectronics via Organogenesis for Tissue-Wide Electrophysiology. Nano Lett. 2019, 19, 5781–5789.
• 57.
  Shroff, S.N.; Das, S.L.; Tseng, H.A.; et al. Voltage Imaging of Cardiac Cells and Tissue Using the Genetically Encoded Voltage Sensor Archon1. iScience 2020, 23, 100974.
• 58.
  Hou, J.H.; Kralj, J.M.; Douglass, A.D.; et al. Simultaneous mapping of membrane voltage and calcium in zebrafish heart in vivo reveals chamber-specific developmental transitions in ionic currents. Front. Physiol. 2014, 5, 344.
• 59.
  Gaspar, J.A.; Doss, M.X.; Hengstler, J.G.; et al. Unique metabolic features of stem cells, cardiomyocytes, and their progenitors. Circ. Res. 2014, 114, 1346–1360.
• 60.
  Lewis-Israeli, Y.R.; Wasserman, A.H.; Gabalski, M.A.; et al. Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease. Nat. Commun. 2021, 12, 5142.
• 61.
  Ferrick, D.A.; Neilson, A.; Beeson, C. Advances in measuring cellular bioenergetics using extracellular flux. Drug Discov. Today 2008, 13, 268–274.
• 62.
  Little, A.C.; Kovalenko, I.; Goo, L.E.; et al. High-content fluorescence imaging with the metabolic flux assay reveals insights into mitochondrial properties and functions. Commun. Biol. 2020, 3, 271.
• 63.
  Ho, B.X.; Pang, J.K.S.; Chen, Y.; et al. Robust generation of human-chambered cardiac organoids from pluripotent stem cells for improved modelling of cardiovascular diseases. Stem Cell Res. Ther. 2022, 13, 529.
• 64.
  Matkovich, S.J. Multiomic approaches to delineate the pathogenesis of cardiac disease. Curr. Opin. Cardiol. 2019, 34, 246–253.
• 65.
  Mantri, M.; Scuderi, G.J.; Abedini-Nassab, R.; et al. Spatiotemporal single-cell RNA sequencing of developing chicken hearts identifies interplay between cellular differentiation and morphogenesis. Nat. Commun. 2021, 12, 1771.
• 66.
  Bowes, J.; Brown, A.J.; Hamon, J.; et al. Reducing safety-related drug attrition: The use of in vitro pharmacological profiling. Nat. Rev. Drug Discov. 2012, 11, 909–922.
• 67.
  Abilez, O.J.; Tzatzalos, E.; Yang, H.; et al. Passive Stretch Induces Structural and Functional Maturation of Engineered Heart Muscle as Predicted by Computational Modeling. Stem Cells 2018, 36, 265–277.
• 68.
  Cho, S.; Lee, C.; Skylar-Scott, M.A.; et al. Reconstructing the heart using iPSCs: Engineering strategies and applications. J. Mol. Cell. Cardiol. 2021, 157, 56–65.
• 69.
  Mannhardt, I.; Saleem, U.; Benzin, A.; et al. Automated Contraction Analysis of Human Engineered Heart Tissue for Cardiac Drug Safety Screening. J. Vis. Exp. 2017, 122, e55461.
• 70.
  Mills, R.J.; Parker, B.L.; Quaife-Ryan, G.A.; et al. Drug Screening in Human PSC-Cardiac Organoids Identifies Pro-proliferative Compounds Acting via the Mevalonate Pathway. Cell Stem Cell 2019, 24, 895–907.
• 71.
  Tian, Y.; Tsujisaka, Y.; Li, V.Y.; et al. Immunosuppressants Tacrolimus and Sirolimus revert the cardiac antifibrotic properties of p38-MAPK inhibition in 3D-multicellular human iPSC-heart organoids. Front. Cell Dev. Biol. 2022, 10, 1001453.
• 72.
  Zhu, L.; Liu, K.; Feng, Q.; et al. Cardiac Organoids: A 3D Technology for Modeling Heart Development and Disease. Stem Cell Rev. Rep. 2022, 18, 2593–2605.