Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perspective
  • Published:

Challenges and opportunities for the next generation of cardiovascular tissue engineering

Nature Methods volume 19, pages 1064–1071 (2022)Cite this article

Subjects

Abstract

Engineered cardiac tissues derived from human induced pluripotent stem cells offer unique opportunities for patient-specific disease modeling, drug discovery and cardiac repair. Since the first engineered hearts were introduced over two decades ago, human induced pluripotent stem cell-based three-dimensional cardiac organoids and heart-on-a-chip systems have now become mainstays in basic cardiovascular research as valuable platforms for investigating fundamental human pathophysiology and development. However, major obstacles remain to be addressed before the field can truly advance toward commercial and clinical translation. Here we provide a snapshot of the state-of-the-art methods in cardiac tissue engineering, with a focus on in vitro models of the human heart. Looking ahead, we discuss major challenges and opportunities in the field and suggest strategies for enabling broad acceptance of engineered cardiac tissues as models of cardiac pathophysiology and testbeds for the development of therapies.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: A scatterplot depicting the trade-off between throughput and maturity in cardiac tissue engineering.
Fig. 2: Illustration of tissue maturity levels that can be achieved by current tissue engineering models.
Fig. 3: Major obstacles and opportunities in cardiac tissue engineering.

Similar content being viewed by others

References

  1. Langer, R. & Vacanti, J. P. Tissue engineering. Science 260, 920–926 (1993).

    Article  CAS  PubMed  Google Scholar 

  2. Kochanek, K. D., Xu, J. & Arias, E. Mortality in the United States, 2019. NCHS Data Brief 395, 1–8 (2020).

  3. Murry, C. E. & MacLellan, W. R. Stem cells and the heart—the road ahead. Science 367, 854–855 (2020).

    Article  CAS  PubMed  Google Scholar 

  4. Vunjak-Novakovic, G., Ronaldson-Bouchard, K. & Radisic, M. Organs-on-a-chip models for biological research. Cell 184, 4597–4611 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kim, H., Kamm, R. D., Vunjak-Novakovic, G. & Wu, J. C. Progress in multicellular human cardiac organoids for clinical applications. Cell Stem Cell 29, 503–514 (2022).

    Article  CAS  PubMed  Google Scholar 

  6. Thomas, D., Choi, S., Alamana, C., Parker, K. K. & Wu, J. C. Cellular and engineered organoids for cardiovascular models. Circ. Res. 130, 1780–1802 (2022).

    Article  CAS  PubMed  Google Scholar 

  7. Cho, S., Lee, C., Skylar-Scott, M. A., Heilshorn, S. C. & Wu, J. C. Reconstructing the heart using iPSCs: engineering strategies and applications. J. Mol. Cell. Cardiol. 157, 56–65 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hofbauer, P., Jahnel, S. M. & Mendjan, S. In vitro models of the human heart. Development 148, dev199672 (2021).

  9. Hofer, M. & Lutolf, M.P. Engineering organoids. Nat. Rev. Mater. 6, 402–420 (2021).

  10. Weinberger, F., Mannhardt, I. & Eschenhagen, T. Engineering cardiac muscle tissue: a maturating field of research. Circ. Res. 120, 1487–1500 (2017).

    Article  CAS  PubMed  Google Scholar 

  11. Huang, N. F. et al. Big bottlenecks in cardiovascular tissue engineering. Commun. Biol. 1, 199 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Ogle, B. M. et al. Distilling complexity to advance cardiac tissue engineering. Sci. Transl. Med. 8, 342ps313 (2016).

    Article  CAS  Google Scholar 

  13. Vunjak-Novakovic, G. et al. Challenges in cardiac tissue engineering. Tissue Eng. Part B Rev. 16, 169–187 (2010).

    Article  PubMed  Google Scholar 

  14. Stein, J. M., Mummery, C. L. & Bellin, M. Engineered models of the human heart: directions and challenges. Stem Cell Reports 16, 2049–2057(2020).

  15. Guo, Y. & Pu, W. T. Cardiomyocyte maturation: new phase in development. Circ. Res. 126, 1086–1106 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. 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 (2019).

    Article  CAS  PubMed  Google Scholar 

  17. Ronaldson-Bouchard, K. et al. Advanced maturation of human cardiac tissue grown from pluripotent stem cells. Nature 556, 239–243 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Campostrini, G., Windt, L. M., van Meer, B. J., Bellin, M. & Mummery, C. L. Cardiac tissues from stem cells: new routes to maturation and cardiac regeneration. Circ. Res. 128, 775–801 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hofbauer, P. et al. Cardioids reveal self-organizing principles of human cardiogenesis. Cell 184, 3299–3317 (2021).

    Article  CAS  PubMed  Google Scholar 

  20. Lewis-Israeli, Y. R. et al. Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease. Nat. Commun. 12, 5142 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Skylar-Scott, M. A. et al. Orthogonally induced differentiation of stem cells for the programmatic patterning of vascularized organoids and bioprinted tissues. Nat. Biomed. Eng. 6, 449–462 (2022).

    Article  CAS  PubMed  Google Scholar 

  22. Radisic, M. et al. Oxygen gradients correlate with cell density and cell viability in engineered cardiac tissue. Biotechnol. Bioeng. 93, 332–343 (2006).

    Article  CAS  PubMed  Google Scholar 

  23. Puente, B. N. et al. The oxygen-rich postnatal environment induces cardiomyocyte cell-cycle arrest through DNA damage response. Cell 157, 565–579 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Rhee, S. et al. Endocardial/endothelial angiocrines regulate cardiomyocyte development and maturation and induce features of ventricular non-compaction. Eur. Heart J. 42, 4264–4276 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Miller, J. S. et al. Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues. Nat. Mater. 11, 768–774 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Redd, M. A. et al. Patterned human microvascular grafts enable rapid vascularization and increase perfusion in infarcted rat hearts. Nat. Commun. 10, 584 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Brassard, J. A., Nikolaev, M., Hubscher, T., Hofer, M. & Lutolf, M. P. Recapitulating macro-scale tissue self-organization through organoid bioprinting. Nat. Mater. 20, 22–29 (2021).

    Article  CAS  PubMed  Google Scholar 

  29. Skylar-Scott, M. A. et al. Biomanufacturing of organ-specific tissues with high cellular density and embedded vascular channels. Sci. Adv. 5, eaaw2459 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Rossi, G. et al. Capturing cardiogenesis in gastruloids. Cell Stem Cell 28, 230–240 (2021).

    Article  CAS  PubMed  Google Scholar 

  31. Wimmer, R. A. et al. Human blood vessel organoids as a model of diabetic vasculopathy. Nature 565, 505–510 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kilpinen, H. et al. Common genetic variation drives molecular heterogeneity in human iPSCs. Nature 546, 370–375 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ortmann, D. et al. Naive pluripotent stem cells exhibit phenotypic variability that is driven by genetic variation. Cell Stem Cell 27, 470–481 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Strano, A., Tuck, E., Stubbs, V. E. & Livesey, F. J. Variable outcomes in neural differentiation of human pscs arise from intrinsic differences in developmental signaling pathways. Cell Rep. 31, 107732 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Burnett, S. D. et al. Population-based toxicity screening in human induced pluripotent stem cell-derived cardiomyocytes. Toxicol. Appl. Pharmacol. 381, 114711 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Mannhardt, I. et al. Comparison of 10 control HPSC lines for drug screening in an engineered heart tissue format. Stem Cell Reports 15, 983–998 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Mannhardt, I. et al. Blinded contractility analysis in hIPSC-cardiomyocytes in engineered heart tissue format: comparison with human atrial trabeculae. Toxicol. Sci. 158, 164–175 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Frangogiannis, N. G. The extracellular matrix in myocardial injury, repair and remodeling. J. Clin. Invest. 127, 1600–1612 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Ott, H. C. et al. Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat. Med. 14, 213–221 (2008).

    Article  CAS  PubMed  Google Scholar 

  40. Herum, K. M., Choppe, J., Kumar, A., Engler, A. J. & McCulloch, A. D. Mechanical regulation of cardiac fibroblast profibrotic phenotypes. Mol. Biol. Cell 28, 1871–1882 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Swift, J. et al. Nuclear lamin-a scales with tissue stiffness and enhances matrix-directed differentiation. Science 341, 1240104 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Martinez-Vidal, L. et al. Causal contributors to tissue stiffness and clinical relevance in urology. Commun. Biol. 4, 1011 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Mascharak, S. et al. Preventing engrailed-1 activation in fibroblasts yields wound regeneration without scarring. Science 372, eaba2374 (2021).

  45. Drakhlis, L. et al. Human heart-forming organoids recapitulate early heart and foregut development. Nat. Biotechnol. 39, 737–746 (2021).

  46. Silva, A. C. et al. Co-emergence of cardiac and gut tissues promotes cardiomyocyte maturation within human iPSC-derived organoids. Cell Stem Cell 28, 2137–2152 (2021).

    Article  CAS  PubMed  Google Scholar 

  47. Bao, X. et al. Directed differentiation and long-term maintenance of epicardial cells derived from human pluripotent stem cells under fully defined conditions. Nat. Protoc. 12, 1890–1900 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Burridge, P. W. et al. Chemically defined generation of human cardiomyocytes. Nat. Methods 11, 855–860 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Lian, X. et al. Efficient differentiation of human pluripotent stem cells to endothelial progenitors via small-molecule activation of wnt signaling. Stem Cell Reports 3, 804–816 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Lian, X. et al. Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt/β-catenin signaling under fully defined conditions. Nat. Protoc. 8, 162–175 (2013).

    Article  CAS  PubMed  Google Scholar 

  51. 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).

    Article  CAS  PubMed  Google Scholar 

  52. Shen, M., Quertermous, T., Fischbein, M. P. & Wu, J. C. Generation of vascular smooth muscle cells from induced pluripotent stem cells: methods, applications, and considerations. Circ Res. 128, 670–686 (2021).

    Article  CAS  PubMed  Google Scholar 

  53. Williams, I. M. & Wu, J. C. Generation of endothelial cells from human pluripotent stem cells. Arterioscler Thromb. Vasc. Biol. 39, 1317–1329 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Zhang, J. et al. Functional cardiac fibroblasts derived from human pluripotent stem cells via second heart field progenitors. Nat. Commun. 10, 2238 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 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 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Zhang, J. Z. et al. A human iPSC double-reporter system enables purification of cardiac lineage subpopulations with distinct function and drug response profiles. Cell Stem Cell 24, 802–811 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Boudou, T. et al. A microfabricated platform to measure and manipulate the mechanics of engineered cardiac microtissues. Tissue Eng. Part A 18, 910–919 (2012).

    Article  CAS  PubMed  Google Scholar 

  59. Huebsch, N. et al. Miniaturized iPS-cell-derived cardiac muscles for physiologically relevant drug response analyses. Sci. Rep. 6, 24726 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Mathur, A. et al. Human iPSC-based cardiac microphysiological system for drug screening applications. Sci. Rep. 5, 8883 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Mohamed, T. M. A. et al. Regulation of cell cycle to stimulate adult cardiomyocyte proliferation and cardiac regeneration. Cell 173, 104–116 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Chen, V. C. et al. Development of a scalable suspension culture for cardiac differentiation from human pluripotent stem cells. Stem Cell Res 15, 365–375 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. 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 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Tavakol, D. N., Fleischer, S. & Vunjak-Novakovic, G. Harnessing organs-on-a-chip to model tissue regeneration. Cell Stem Cell 28, 993–1015 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Mawad, D. et al. A conducting polymer with enhanced electronic stability applied in cardiac models. Sci. Adv. 2, e1601007 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Wei, K. et al. Epicardial FSTL1 reconstitution regenerates the adult mammalian heart. Nature 525, 479–485 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Fei, P. et al. Cardiac light-sheet fluorescent microscopy for multi-scale and rapid imaging of architecture and function. Sci. Rep. 6, 22489 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Lind, J. U. et al. Instrumented cardiac microphysiological devices via multimaterial three-dimensional printing. Nat. Mater. 16, 303–308 (2017).

    Article  CAS  PubMed  Google Scholar 

  69. Michas, C. et al. Engineering a living cardiac pump on a chip using high-precision fabrication. Sci. Adv. 8, eabm3791 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  70. McAleer, C. W. et al. Multi-organ system for the evaluation of efficacy and off-target toxicity of anticancer therapeutics. Sci. Transl. Med. 11, eaav1386 (2019).

  71. Ronaldson-Bouchard, K. et al. A multi-organ chip with matured tissue niches linked by vascular flow. Nat. Biomed. Eng. 6, 351–371 (2022).

    Article  CAS  PubMed  Google Scholar 

  72. Ribeiro, A. J. et al. Contractility of single cardiomyocytes differentiated from pluripotent stem cells depends on physiological shape and substrate stiffness. Proc. Natl Acad. Sci. USA 112, 12705–12710 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Ma, Z. et al. Self-organizing human cardiac microchambers mediated by geometric confinement. Nat. Commun. 6, 7413 (2015).

    Article  CAS  PubMed  Google Scholar 

  74. Richards, D. J. et al. Human cardiac organoids for the modelling of myocardial infarction and drug cardiotoxicity. Nat. Biomed. Eng. 4, 446–462 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Bliley, J. M. et al. Dynamic loading of human engineered heart tissue enhances contractile function and drives a desmosome-linked disease phenotype. Sci. Transl. Med. 13, eabd1817 (2021).

  76. Eschenhagen, T. et al. Three-dimensional reconstitution of embryonic cardiomyocytes in a collagen matrix: a new heart muscle model system. FASEB J. 11, 683–694 (1997).

    Article  CAS  PubMed  Google Scholar 

  77. Hansen, A. et al. Development of a drug screening platform based on engineered heart tissue. Circ. Res. 107, 35–44 (2010).

    Article  CAS  PubMed  Google Scholar 

  78. MacQueen, L. A. et al. A tissue-engineered scale model of the heart ventricle. Nat. Biomed. Eng. 2, 930–941 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Nunes, S. S. et al. Biowire: a platform for maturation of human pluripotent stem cell-derived cardiomyocytes. Nat. Methods 10, 781–787 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. 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).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Zhao, Y. et al. A platform for generation of chamber-specific cardiac tissues and disease modeling. Cell 176, 913–927 e918 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Zimmermann, W. H. et al. Tissue engineering of a differentiated cardiac muscle construct. Circ. Res. 90, 223–230 (2002).

    Article  CAS  PubMed  Google Scholar 

  83. Huebsch, N. et al. Metabolically driven maturation of human-induced-pluripotent-stem-cell-derived cardiac microtissues on microfluidic chips. Nat. Biomed. Eng. 6, 372–388 (2022).

    Article  CAS  PubMed  Google Scholar 

  84. Legant, W. R. et al. Microfabricated tissue gauges to measure and manipulate forces from 3D microtissues. Proc. Natl Acad. Sci. USA 106, 10097–10102 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Kupfer, M. E. et al. In situ expansion, differentiation and electromechanical coupling of human cardiac muscle in a 3D bioprinted, chambered organoid. Circ. Res. 127, 207–224 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Lee, A. et al. 3D bioprinting of collagen to rebuild components of the human heart. Science 365, 482–487 (2019).

    Article  CAS  PubMed  Google Scholar 

  87. Pati, F. et al. Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink. Nat. Commun. 5, 3935 (2014).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work is supported by National Institutes of Health grants F32 HL152483 (to S.C.); R01 HL113006, R01 HL141371, R01 HL141851, R01 HL146690, R01 HL150693 and R01 HL163680 (to J.C.W.); and UH3 EB025765, P41 EB027062 and 3R01 HL076485 (to G.V.-N.).

Author information

Authors and Affiliations

  1. Stanford Cardiovascular Institute, Stanford, CA, USA

    Sangkyun Cho & Joseph C. Wu

  2. Department of Medicine, Division of Cardiovascular Medicine, Stanford, CA, USA

    Sangkyun Cho & Joseph C. Wu

  3. Molecular & Cell Biophysics Laboratory, University of Pennsylvania, Philadelphia, PA, USA

    Dennis E. Discher

  4. Pennsylvania Muscle Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Dennis E. Discher

  5. Department of Biomedical Engineering, Columbia University, New York, NY, USA

    Kam W. Leong & Gordana Vunjak-Novakovic

  6. Department of Medicine, Columbia University, New York, NY, USA

    Gordana Vunjak-Novakovic

Authors
  1. Sangkyun Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dennis E. Discher
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kam W. Leong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gordana Vunjak-Novakovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Joseph C. Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S.C. researched data, designed the figures and wrote the manuscript. S.C., D.E.D., K.W.L., G.V.-N. and J.C.W. contributed substantially to the discussion of content, and reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Joseph C. Wu.

Ethics declarations

Competing interests

J.C.W. is a cofounder of Greenstone Biosciences and G.V.-N. is a cofounder of Tara Biosystems; however, the work presented here is independent. The other authors report no competing interests.

Peer review

Peer review information

Nature Methods thanks Aitor Aguirre, Milena Bellin, and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Nina Vogt, in collaboration with the Nature Methods team.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cho, S., Discher, D.E., Leong, K.W. et al. Challenges and opportunities for the next generation of cardiovascular tissue engineering. Nat Methods 19, 1064–1071 (2022). https://doi.org/10.1038/s41592-022-01591-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41592-022-01591-3

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research