DOI QR코드

DOI QR Code

Electrophysiological insights with brain organoid models: a brief review

  • Rian Kang (Institute of Quantum Biophysics, Sungkyunkwan University) ;
  • Soomin Park (Institute of Quantum Biophysics, Sungkyunkwan University) ;
  • Saewoon Shin (Institute of Quantum Biophysics, Sungkyunkwan University) ;
  • Gyusoo Bak (Institute of Quantum Biophysics, Sungkyunkwan University) ;
  • Jong-Chan Park (Institute of Quantum Biophysics, Sungkyunkwan University)
  • Received : 2024.04.28
  • Accepted : 2024.06.19
  • Published : 2024.07.31

Abstract

Brain organoid is a three-dimensional (3D) tissue derived from stem cells such as induced pluripotent stem cells (iPSCs) embryonic stem cells (ESCs) that reflect real human brain structure. It replicates the complexity and development of the human brain, enabling studies of the human brain in vitro. With emerging technologies, its application is various, including disease modeling and drug screening. A variety of experimental methods have been used to study structural and molecular characteristics of brain organoids. However, electrophysiological analysis is necessary to understand their functional characteristics and complexity. Although electrophysiological approaches have rapidly advanced for monolayered cells, there are some limitations in studying electrophysiological and neural network characteristics due to the lack of 3D characteristics. Herein, electrophysiological measurement and analytical methods related to neural complexity and 3D characteristics of brain organoids are reviewed. Overall, electrophysiological understanding of brain organoids allows us to overcome limitations of monolayer in vitro cell culture models, providing deep insights into the neural network complex of the real human brain and new ways of disease modeling.

Keywords

Acknowledgement

This work was supported by a grant of Ministry of Education of the Republic of Korea and the National Research Foundation of Korea (RS-2023-00266110). The graphical arts are generated by Biorender.com under Jong-Chan Park, Ph.D.

References

  1. Stiles J and Jernigan TL (2010) The basics of brain development. Neuropsychol Rev 20, 327-348  https://doi.org/10.1007/s11065-010-9148-4
  2. Kelava I and Lancaster MA (2016) Stem cell models of human brain development. Cell Stem Cell 18, 736-748  https://doi.org/10.1016/j.stem.2016.05.022
  3. Zhao X and Bhattacharyya A (2018) Human models are needed for studying human neurodevelopmental disorders. Am J Hum Genet 103, 829-857  https://doi.org/10.1016/j.ajhg.2018.10.009
  4. Bose R, Banerjee S and Dunbar GL (2021) Modeling neurological disorders in 3D organoids using human-derived pluripotent stem cells. Front Cell Dev Biol 9, 640212 
  5. Lee CT, Bendriem RM, Wu WW and Shen RF (2017) 3D brain organoids derived from pluripotent stem cells: promising experimental models for brain development and neurodegenerative disorders. J Biomed Sci 24, 59 
  6. Smirnova L and Hartung T (2024) The promise and potential of brain organoids. Adv Healthc Mater, e2302745 
  7. Pasca AM, Sloan SA, Clarke LE et al (2015) Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture. Nat Methods 12, 671-678  https://doi.org/10.1038/nmeth.3415
  8. Lancaster MA and Knoblich JA (2014) Generation of cerebral organoids from human pluripotent stem cells. Nat Protoc 9, 2329-2340  https://doi.org/10.1038/nprot.2014.158
  9. Kanton S, Boyle MJ, He Z et al (2019) Organoid single-cell genomic atlas uncovers human-specific features of brain development. Nature 574, 418-422  https://doi.org/10.1038/s41586-019-1654-9
  10. Gordon A, Yoon SJ, Tran SS et al (2021) Long-term maturation of human cortical organoids matches key early postnatal transitions. Nat Neurosci 24, 331-342  https://doi.org/10.1038/s41593-021-00802-y
  11. Qian X, Su Y, Adam CD et al (2020) Sliced human cortical organoids for modeling distinct cortical layer formation. Cell Stem Cell 26, 766-781 e769 
  12. Egervari G, Kozlenkov A, Dracheva S and Hurd YL (2019) Molecular windows into the human brain for psychiatric disorders. Mol Psychiatry 24, 653-673  https://doi.org/10.1038/s41380-018-0125-2
  13. Samarasinghe RA, Miranda OA, Buth JE et al (2021) Identification of neural oscillations and epileptiform changes in human brain organoids. Nat Neurosci 24, 1488-1500  https://doi.org/10.1038/s41593-021-00906-5
  14. Sharf T, van der Molen T, Glasauer SMK et al (2022) Functional neuronal circuitry and oscillatory dynamics in human brain organoids. Nat Commun 13, 4403 
  15. Kim SH and Chang MY (2023) Application of human brain organoids-opportunities and challenges in modeling human brain development and neurodevelopmental diseases. Int J Mol Sci 24, 12528 
  16. Kim J, Lee S, Lee J et al (2022) Neurotoxicity of phenylalanine on human iPSC-derived cerebral organoids. Mol Genet Metab 136, 132-144  https://doi.org/10.1016/j.ymgme.2022.04.005
  17. Cho YH, Ro EJ, Yoon JS et al (2020) 5-FU promotes stemness of colorectal cancer via p53-mediated WNT/beta-catenin pathway activation. Nat Commun 11, 5321 
  18. Chen HI, Song H and Ming GL (2019) Applications of human brain organoids to clinical problems. Dev Dyn 248, 53-64  https://doi.org/10.1002/dvdy.24662
  19. Chang Y, Kim J, Park H, Choi H and Kim J (2020) Modelling neurodegenerative diseases with 3D brain organoids. Biol Rev Camb Philos Soc 95, 1497-1509  https://doi.org/10.1111/brv.12626
  20. Villa C, Combi R, Conconi D and Lavitrano M (2021) Patient-derived induced pluripotent stem cells (iPSCs) and cerebral organoids for drug screening and development in autism spectrum disorder: opportunities and challenges. Pharmaceutics 13, 2-280  https://doi.org/10.3390/pharmaceutics13020280
  21. Lee C, Willerth SM and Nygaard HB (2020) The use of patient-derived induced pluripotent stem cells for Alzheimer's disease modeling. Prog Neurobiol 192, 101804 
  22. Park JC, Jang SY, Lee D et al (2021) A logical network-based drug-screening platform for Alzheimer's disease representing pathological features of human brain organoids. Nat Commun 12, 280 
  23. Choi H, Kim HJ, Yang J et al (2020) Acetylation changes tau interactome to degrade tau in Alzheimer's disease animal and organoid models. Aging Cell 19, e13081 
  24. Park JC, Barahona-Torres N, Jang SY et al (2022) Multi-omics-based autophagy-related untypical subtypes in patients with cerebral amyloid pathology. Adv Sci (Weinh) 9, e2201212 
  25. Di Lullo E and Kriegstein AR (2017) The use of brain organoids to investigate neural development and disease. Nat Rev Neurosci 18, 573-584  https://doi.org/10.1038/nrn.2017.107
  26. Fietz SA, Kelava I, Vogt J et al (2010) OSVZ progenitors of human and ferret neocortex are epithelial-like and expand by integrin signaling. Nat Neurosci 13, 690-699  https://doi.org/10.1038/nn.2553
  27. Berridge MJ, Lipp P and Bootman MD (2000) The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 1, 11-21  https://doi.org/10.1038/35036035
  28. Sakaguchi H, Ozaki Y, Ashida T et al (2019) Self-organized synchronous calcium transients in a cultured human neural network derived from cerebral organoids. Stem Cell Reports 13, 458-473  https://doi.org/10.1016/j.stemcr.2019.05.029
  29. de Melo Reis RA, Freitas HR and de Mello FG (2020) Cell calcium imaging as a reliable method to study neuronglial circuits. Front Neurosci 14, 569361 
  30. Landry CR, Yip MC, Zhou Y et al (2023) Electrophysiological and morphological characterization of single neurons in intact human brain organoids. J Neurosci Methods 394, 109898 
  31. Tasnim K and Liu J (2022) Emerging bioelectronics for brain organoid electrophysiology. J Mol Biol 434, 167165 
  32. Sivitilli AA, Gosio JT, Ghoshal B et al (2020) Robust production of uniform human cerebral organoids from pluripotent stem cells. Life Sci Alliance 3, 5 
  33. Trujillo CA, Gao R, Negraes PD et al (2019) Complex oscillatory waves emerging from cortical organoids model early human brain network development. Cell Stem Cell 25, 558-569 e557 
  34. Yokoi R, Shibata M, Odawara A et al (2021) Analysis of signal components < 500 Hz in brain organoids coupled to microelectrode arrays: a reliable test-bed for preclinical seizure liability assessment of drugs and screening of antiepileptic drugs. Biochem Biophys Rep 28, 101148 
  35. Huang Q, Tang B, Romero JC et al (2022) Shell microelectrode arrays (MEAs) for brain organoids. Sci Adv 8, eabq5031 
  36. Qian X, Song H and Ming GL (2019) Brain organoids: advances, applications and challenges. Development 146, 8-dev166074 
  37. Le Floch P, Li Q, Lin Z et al (2022) Stretchable Mesh Nanoelectronics for 3D single-cell chronic electrophysiology from developing brain organoids. Adv Mater 34, e2106829 
  38. Li Q, Nan K, Le Floch P et al (2019) Cyborg organoids: implantation of nanoelectronics via organogenesis for tissue-wide electrophysiology. Nano Lett 19, 5781-5789  https://doi.org/10.1021/acs.nanolett.9b02512
  39. Soscia DA, Lam D, Tooker AC et al (2020) A flexible 3-dimensional microelectrode array for in vitro brain models. Lab Chip 20, 901-911  https://doi.org/10.1039/C9LC01148J
  40. Maroso M (2023) A quest into the human brain. Science 382, 166-167  https://doi.org/10.1126/science.adl0913
  41. Zimmer C (2011) 100 trillion connections. Sci Am 304, 58-63  https://doi.org/10.1038/scientificamerican0111-58
  42. Herculano-Houzel S (2012) The remarkable, yet not extraordinary, human brain as a scaled-up primate brain and its associated cost. Proc Natl Acad Sci U S A 109 Suppl 1, 10661-10668  https://doi.org/10.1073/pnas.1201895109
  43. Cai H, Ao Z, Tian C et al (2023) Brain organoid computing for artificial intelligence. bioRxiv 28, 530502 
  44. Morales Pantoja IE, Smirnova L, Muotri AR et al (2023) First organoid intelligence (OI) workshop to form an OI community. Front Artif Intell 6, 1116870 
  45. Reardon S (2020) Can lab-grown brains become conscious? Nature 586, 658-661  https://doi.org/10.1038/d41586-020-02986-y
  46. Saglam-Metiner P, Yildirim E, Dincer C, Basak O and Yesil-Celiktas O (2024) Humanized brain organoids-on-chip integrated with sensors for screening neuronal activity and neurotoxicity. Mikrochim Acta 191, 71 
  47. Castiglione H, Vigneron PA, Baquerre C, Yates F, Rontard J and Honegger T (2022) Human brain organoids-on-chip: advances, challenges, and perspectives for preclinical applications. Pharmaceutics 14, 11-2301  https://doi.org/10.3390/pharmaceutics14112301
  48. Khadir A, Maghareh M, Sasani Ghamsari S and Beigzadeh B (2023) Brain activity characteristics of RGB stimulus: an EEG study. Sci Rep 13, 18988 
  49. Qiu W, Bouakaz A, Konofagou EE and Zheng H (2021) Ultrasound for the brain: a review of physical and engineering principles, and clinical applications. IEEE Trans Ultrason Ferroelectr Freq Control 68, 6-20  https://doi.org/10.1109/TUFFC.2020.3019932
  50. Xian QX, Qiu ZH, Murugappan S et al (2023) Modulation of deep neural circuits with sonogenetics. Proceedings of the NAS 120, 22-e2220575120