DOI QR코드

DOI QR Code

Lung Organoid on a Chip: A New Ensemble Model for Preclinical Studies

  • Hyung-Jun Kim (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Sohyun Park (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Seonghyeon Jeong (Department of Internal Medicine, Seoul National University College of Medicine) ;
  • Jihoon Kim (Department of Medical and Biological Sciences, The Catholic University of Korea) ;
  • Young-Jae Cho (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital)
  • 투고 : 2023.06.15
  • 심사 : 2023.09.08
  • 발행 : 2024.02.28

초록

The lung is a complex organ comprising a branched airway that connects the large airway and millions of terminal gas-exchange units. Traditional pulmonary biomedical research by using cell line model system have limitations such as lack of cellular heterogeneity, animal models also have limitations including ethical concern, race-to-race variations, and physiological differences found in vivo. Organoids and on-a-chip models offer viable solutions for these issues. Organoids are three-dimensional, self-organized construct composed of numerous cells derived from stem cells cultured with growth factors required for the maintenance of stem cells. On-a-chip models are biomimetic microsystems which are able to customize to use microfluidic systems to simulate blood flow in blood channels or vacuum to simulate human breathing. This review summarizes the key components and previous biomedical studies conducted on lung organoids and lung-on-a-chip models, and introduces potential future applications. Considering the importance and benefits of these model systems, we believe that the system will offer better platform to biomedical researchers on pulmonary diseases, such as emerging viral infection, progressive fibrotic pulmonary diseases, or primary or metastatic lung cancer.

키워드

과제정보

This paper was supported by the Seoul National University Bundang Hospital research fund (No. 02-2021-0007) and the National Research Foundation of Korea Grant funded by the Korean Government (2021K1A4A7A02097757).

참고문헌

  1. Hogan BL, Barkauskas CE, Chapman HA, et al. Repair and regeneration of the respiratory system: complexity, plasticity, and mechanisms of lung stem cell function. Cell Stem Cell 2014;15:123-138
  2. Gkatzis K, Taghizadeh S, Huh D, Stainier DYR, Bellusci S. Use of three-dimensional organoids and lung-on-a-chip methods to study lung development, regeneration and disease. Eur Respir J 2018;52:1800876
  3. Miller AJ, Dye BR, Ferrer-Torres D, et al. Generation of lung organoids from human pluripotent stem cells in vitro. Nat Protoc 2019;14:518-540
  4. Wilkinson DC, Alva-Ornelas JA, Sucre JM, et al. Development of a three-dimensional bioengineering technology to generate lung tissue for personalized disease modeling. Stem Cells Transl Med 2017;6:622-633
  5. Kim J, Koo BK, Knoblich JA. Human organoids: model systems for human biology and medicine. Nat Rev Mol Cell Biol 2020;21:571-584
  6. Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DE. Reconstituting organ-level lung functions on a chip. Science 2010;328:1662-1668
  7. Clevers H. Stem cells. What is an adult stem cell? Science 2015;350:1319-1320
  8. Tian L, Gao J, Garcia IM, Chen HJ, Castaldi A, Chen YW. Human pluripotent stem cell-derived lung organoids: potential applications in development and disease modeling. Wiley Interdiscip Rev Dev Biol 2021;10:e399
  9. Rock JR, Onaitis MW, Rawlins EL, et al. Basal cells as stem cells of the mouse trachea and human airway epithelium. Proc Natl Acad Sci U S A 2009;106:12771-12775
  10. Hofer M, Lutolf MP. Engineering organoids. Nat Rev Mater 2021;6:402-420
  11. Dye BR, Dedhia PH, Miller AJ, et al. A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids. Elife 2016; :e19732
  12. Orkin RW, Gehron P, McGoodwin EB, Martin GR, Valentine T, Swarm R. A murine tumor producing a matrix of basement membrane. J Exp Med 1977;145:204-220
  13. Aisenbrey EA, Murphy WL. Synthetic alternatives to Matrigel. Nat Rev Mater 2020;5:539-551
  14. Lee HJ, Mun S, Pham DM, Kim P. Extracellular matrixased hydrogels to tailoring tumor organoids. ACS Biomater Sci Eng 2021;7:4128-4135
  15. Gupta N, Liu JR, Patel B, Solomon DE, Vaidya B, Gupta V. Microfluidics-based 3D cell culture models: utility in novel drug discovery and delivery research. Bioeng Transl Med 2016;1:63-81
  16. Jain A, Barrile R, van der Meer AD, et al. Primary human lung alveolus-on-a-chip model of intravascular thrombosis for assessment of therapeutics. Clin Pharmacol Ther 2018;03:332-340
  17. Ding S, Zhang H, Wang X. Microfluidic-chip-integrated biosensors for lung disease models. Biosensors (Basel) 2021;1:456.
  18. Munta K, Gopal PB, Vigg A. Invasive aspergillosis in near drowning nonneutropenic patient. Indian J Crit Care Med 2015;19:739-742
  19. Blank F, Rothen-Rutishauser B, Gehr P. Dendritic cells and macrophages form a transepithelial network against foreign particulate antigens. Am J Respir Cell Mol Biol 2007;36:669-677
  20. Lenz AG, Karg E, Brendel E, et al. Inflammatory and oxidative stress responses of an alveolar epithelial cell line to airborne zinc oxide nanoparticles at the air-liquid interface: a comparison with conventional, submerged cell-culture conditions. Biomed Res Int 2013;2013:652632
  21. Wu J, Wang Y, Liu G, Jia Y, Yang J, Shi J, et al. Characterization of air-liquid interface culture of A549 alveolar epithelial cells. Braz J Med Biol Res 2017;51:e6950
  22. Upadhyay S, Palmberg L. Air-liquid interface: relevant in vitro models for investigating air pollutant-induced pulmonary toxicity. Toxicol Sci 2018;164:21-30
  23. Nalayanda DD, Puleo C, Fulton WB, Sharpe LM, Wang TH, Abdullah F. An open-access microfluidic model for lung-specific functional studies at an air-liquid interface. Biomed Microdevices 2009;11:1081-1089
  24. Lamers MM, van der Vaart J, Knoops K, et al. An organoid-derived bronchioalveolar model for SARS-CoV-2 infection of human alveolar type II-like cells. EMBO J 2021;40:105912
  25. Si L, Bai H, Rodas M, et al. A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics. Nat Biomed Eng 2021;5:815-829
  26. Suezawa T, Kanagaki S, Moriguchi K, et al. Disease modeling of pulmonary fibrosis using human pluripotent stem cell-erived alveolar organoids. Stem Cell Reports 2021;16:973-2987
  27. Plebani R, Potla R, Soong M, et al. Modeling pulmonary cystic fibrosis in a human lung airway-on-a-chip. J Cyst Fibros 2022;21:606-615
  28. Kim M, Mun H, Sung CO, et al. Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening. Nat Commun 2019;10:3991
  29. Shi R, Radulovich N, Ng C, et al. Organoid cultures as preclinical models of non-small cell lung cancer. Clin Cancer Res 2020;26:1162-1174
  30. Hu Y, Sui X, Song F, et al. Lung cancer organoids analyzed on microwell arrays predict drug responses of patients within a week. Nat Commun 2021;12:2581
  31. Park S, Kim TH, Kim SH, You S, Jung Y. Three-dimensional vascularized lung cancer-on-a-chip with lung extracellular matrix hydrogels for in vitro screening. Cancers (Basel) 2021;13:3930
  32. Gjorevski N, Lutolf MP. Synthesis and characterization of well-defined hydrogel matrices and their application to intestinal stem cell and organoid culture. Nat Protoc 2017;12:263-2274
  33. Mammoto A, Mammoto T. Vascular niche in lung alveolar development, homeostasis, and regeneration. Front Bioeng Biotechnol 2019;7:318
  34. Sobrino A, Phan DT, Datta R, et al. 3D microtumors in vitro supported by perfused vascular networks. Sci Rep 2016;6:31589
  35. van Engeland NCA, Pollet AMAO, den Toonder JMJ, Bouten CVC, Stassen OMJA, Sahlgren CM. A biomimetic microfluidic model to study signalling between endothelial and vascular smooth muscle cells under hemodynamic conditions. Lab Chip 2018;18:1607-1620
  36. Stewart RH. A modern view of the interstitial space in health and disease. Front Vet Sci 2020;7:609583
  37. Li G, Fan Y, Lai Y, et al. Coronavirus infections and immune responses. J Med Virol 2020;92:424-432
  38. Shrestha J, Razavi Bazaz S, Aboulkheyr Es H, et al. Lung-on-a-chip: the future of respiratory disease models and pharmacological studies. Crit Rev Biotechnol 2020;40:13-230
  39. Crapo JD, Barry BE, Gehr P, Bachofen M, Weibel ER. Cell number and cell characteristics of the normal human lung. Am Rev Respir Dis 1982;126:332-337
  40. Barkauskas CE, Chung MI, Fioret B, Gao X, Katsura H, Hogan BL. Lung organoids: current uses and future promise. Development 2017;144:986-997