International Journal of Stem Cells

Korean Society for Stem Cell Research (한국줄기세포학회)
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Essential Guidelines for Manufacturing and Application of Organoids

  • Sun-Ju Ahn (Department of Biophysics, Sungkyunkwan University) ;
  • Sungin Lee (Institute of Quantum Biophysics, Sungkyunkwan University) ;
  • Dayeon Kwon (Institute of Quantum Biophysics, Sungkyunkwan University) ;
  • Sejeong Oh (Institute of Quantum Biophysics, Sungkyunkwan University) ;
  • Chihye Park (Institute of Quantum Biophysics, Sungkyunkwan University) ;
  • Sooyeon Jeon (Institute of Quantum Biophysics, Sungkyunkwan University) ;
  • Jin Hee Lee (Organoid Standards Initiative) ;
  • Tae Sung Kim (Organoid Standards Initiative) ;
  • Il Ung Oh (Organoid Standards Initiative)
  • Received : 2024.04.08
  • Accepted : 2024.05.08
  • Published : 2024.05.30
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Abstract

An organoid is a self-organized three-dimensional structure derived from stem cells that mimics the structure, cell composition, and functional characteristics of specific organs and tissues and is used for evaluating the safety and effectiveness of drugs and the toxicity of industrial chemicals. Organoid technology is a new methodology that could replace testing on animals testing and accelerate development of precision and regenerative medicine. However, large variations in production can occur between laboratories with low reproducibility of the production process and no internationally agreed standards for quality evaluation factors at endpoints. To overcome these barriers that hinder the regulatory acceptance and commercialization of organoids, Korea established the Organoid Standards Initiative in September 2023 with various stakeholders, including industry, academia, regulatory agencies, and standard development experts, through public and private partnerships. This developed general guidelines for organoid manufacturing and quality evaluation and for quality evaluation guidelines for organoid-specific manufacturing for the liver, intestines, and heart through extensive evidence analysis and consensus among experts. This report is based on the common standard guideline v1.0, which is a general organoid manufacturing and quality evaluation to promote the practical use of organoids. This guideline does not focus on specific organoids or specific contexts of use but provides guidance to organoid makers and users on materials, procedures, and essential quality assessment methods at end points that are essential for organoid production applicable at the current technology level.

Keywords

Acknowledgement

We thank those who contributed to the successful completion of this manuscript. We would like to thank first the Ministry of Food and Drug Safety, OSI committee chairs and members, and the Institute of Quantum Biophysics, especially, Professor Luke Lee for his invaluable insights.

References

  1. de Souza N. Organoids. Nat Methods 2018;15:23
  2. Derouet MF, Allen J, Wilson GW, et al. Towards personalized induction therapy for esophageal adenocarcinoma: organoids derived from endoscopic biopsy recapitulate the pre-treatment tumor. Sci Rep 2020;10:14514
  3. Schmeisser S, Miccoli A, von Bergen M, et al. New approach methodologies in human regulatory toxicology - not if, but how and when! Environ Int 2023;178:108082
  4. Griffith LG, Swartz MA. Capturing complex 3D tissue physiology in vitro. Nat Rev Mol Cell Biol 2006;7:211-224
  5. Nims RW, Sykes G, Cottrill K, Ikonomi P, Elmore E. Short tandem repeat profiling: part of an overall strategy for reducing the frequency of cell misidentification. In Vitro Cell Dev Biol Anim 2010;46:811-819
  6. Korch CT, Hall EM, Dirks WG, et al. ANSI/ATCC ASN0002-2022. Human cell line authentication: standardization of short tandem repeat (STR) profiling - revised 2022. American National Standards Institute (ANSI); 2022
  7. Pasquier L, Fradin M, Cherot E, et al. Karyotype is not dead (yet)! Eur J Med Genet 2016;59:11-15
  8. Wiszniewska J, Bi W, Shaw C, et al. Combined array CGH plus SNP genome analyses in a single assay for optimized clinical testing. Eur J Hum Genet 2014;22:79-87
  9. Sukswai N, Khoury JD. Immunohistochemistry innovations for diagnosis and tissue-based biomarker detection. Curr Hematol Malig Rep 2019;14:368-375
  10. Givan AL. Flow cytometry: first principles. 2nd ed. Wiley-Liss; 2001
  11. Innis MA, Gelfand DH, Sninsky JJ, White TJ. PCR protocols: a guide to methods and applications. Academic Press; 1990
  12. Zhang Q, Han Z, Zhu Y, Chen J, Li W. The role and specific mechanism of OCT4 in cancer stem cells: a review. Int J Stem Cells 2020;13:312-325
  13. Na J, Plews J, Li J, et al. Molecular mechanisms of pluripotency and reprogramming. Stem Cell Res Ther 2010;1:33
  14. Evron A, Goldman S, Shalev E. Human amniotic epithelial cells cultured in substitute serum medium maintain their stem cell characteristics for up to four passages. Int J Stem Cells 2011;4:123-132
  15. Wang X, Wang S, Guo B, et al. Human primary epidermal organoids enable modeling of dermatophyte infections. Cell Death Dis 2021;12:35
  16. Mikels AJ, Nusse R. Wnts as ligands: processing, secretion and reception. Oncogene 2006;25:7461-7468
  17. Liu J, Xiao Q, Xiao J, et al. Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities. Signal Transduct Target Ther 2022;7:3
  18. Sarapura VD, Gordon DF, Samuels MH. Thyroid-stimulating hormone. In: Melmed S, editor. The pituitary. 3rd ed. Academic Press; 2011. 167-203
  19. Bostrom H, Gritli-Linde A, Betsholtz C. PDGF-A/PDGF alpha-receptor signaling is required for lung growth and the formation of alveoli but not for early lung branching morphogenesis. Dev Dyn 2002;223:155-162
  20. Kleinman HK, Luckenbill-Edds L, Cannon FW, Sephel GC. Use of extracellular matrix components for cell culture. Anal Biochem 1987;166:1-13
  21. Kleinman HK, Philp D, Hoffman MP. Role of the extracellular matrix in morphogenesis. Curr Opin Biotechnol 2003;14:526-532
  22. Kim J, Koo BK, Knoblich JA. Human organoids: model systems for human biology and medicine. Nat Rev Mol Cell Biol 2020;21:571-584
  23. Harrison SP, Baumgarten SF, Verma R, Lunov O, Dejneka A, Sullivan GJ. Liver organoids: recent developments, limitations and potential. Front Med (Lausanne) 2021;8:574047
  24. Kong J, Wen S, Cao W, et al. Lung organoids, useful tools for investigating epithelial repair after lung injury. Stem Cell Res Ther 2021;12:95
  25. Dye BR, Hill DR, Ferguson MA, et al. In vitro generation of human pluripotent stem cell derived lung organoids. Elife 2015;4:e05098
  26. McCauley KB, Hawkins F, Serra M, Thomas DC, Jacob A, Kotton DN. Efficient derivation of functional human airway epithelium from pluripotent stem cells via temporal regulation of Wnt signaling. Cell Stem Cell 2017;20:844-857.e6
  27. Kim J, Sullivan GJ, Park IH. How well do brain organoids capture your brain? iScience 2021;24:102063
  28. Gabbin B, Meraviglia V, Angenent ML, et al. Heart and kidney organoids maintain organ-specific function in a microfluidic system. Mater Today Bio 2023;23:100818
  29. Mun SJ, Ryu JS, Lee MO, et al. Generation of expandable human pluripotent stem cell-derived hepatocyte-like liver organoids. J Hepatol 2019;71:970-985