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Current strategies using 3D organoids to establish in vitro maternal-embryonic interaction

  • Islam Mohamed Saadeldin (Comparative Medicine Department, King Faisal Specialist Hospital and Research Centre) ;
  • Seif Ehab (Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology) ;
  • Ahmed Elsayed Noreldin (Department of Histology and Cytology, Faculty of Veterinary Medicine, Damanhour University, the Scientific Campus) ;
  • Ayman Abdel-Aziz Swelum (Department of Animal Production, College of Food and Agriculture Sciences, King Saud University) ;
  • Seonggyu Bang (College of Veterinary Medicine, Chungnam National University) ;
  • Hyejin Kim (Division in Biomedical Art, Department of Fine Art, Incheon Catholic University Graduate School) ;
  • Ki Young Yoon (Department of Companion Animal, Shingu College) ;
  • Sanghoon Lee (College of Veterinary Medicine, Chungnam National University) ;
  • Jongki Cho (College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University)
  • 투고 : 2024.01.07
  • 심사 : 2024.03.28
  • 발행 : 2024.05.31

초록

Importance: The creation of robust maternal-embryonic interactions and implantation models is important for comprehending the early stages of embryonic development and reproductive disorders. Traditional two-dimensional (2D) cell culture systems often fail to accurately mimic the highly complex in vivo conditions. The employment of three-dimensional (3D) organoids has emerged as a promising strategy to overcome these limitations in recent years. The advancements in the field of organoid technology have opened new avenues for studying the physiology and diseases affecting female reproductive tract. Observations: This review summarizes the current strategies and advancements in the field of 3D organoids to establish maternal-embryonic interaction and implantation models for use in research and personalized medicine in assisted reproductive technology. The concepts of endometrial organoids, menstrual blood flow organoids, placental trophoblast organoids, stem cell-derived blastoids, and in vitro-generated embryo models are discussed in detail. We show the incorportaion of organoid systems and microfluidic technology to enhance tissue performance and precise management of the cellular surroundings. Conclusions and Relevance: This review provides insights into the future direction of modeling maternal-embryonic interaction research and its combination with other powerful technologies to interfere with this dialogue either by promoting or hindering it for improving fertility or methods for contraception, respectively. The merging of organoid systems with microfluidics facilitates the creation of sophisticated and functional organoid models, enhancing insights into organ development, disease mechanisms, and personalized medical investigations.

키워드

과제정보

This work was supported by the Ministry of Science and ICT through the National Research Foundation of Korea (NRF) (grant numbers:2021R1A2C2009294 and 2022R1I1A1A01065412) and the Brain Pool Program (grant number:2021H1D3A2A02040098). The funding bodies have no role in the design of the study or the analysis and interpretation of data.

참고문헌

  1. Laufer N, Simon A. Recurrent implantation failure: current update and clinical approach to an ongoing challenge. Fertil Steril. 2012;97(5):1019-1020.
  2. Wen L, Tang F. Organoid research on human early development and beyond. Med Rev (2021). 2022;2(5):512-523.
  3. Fitzgerald HC, Schust DJ, Spencer TE. In vitro models of the human endometrium: evolution and application for women's health. Biol Reprod. 2021;104(2):282-293.
  4. Aplin JD, Ruane PT. Embryo-epithelium interactions during implantation at a glance. J Cell Sci. 2017;130(1):15-22.
  5. Rossi G, Manfrin A, Lutolf MP. Progress and potential in organoid research. Nat Rev Genet. 2018;19(11):671-687.
  6. Corro C, Novellasdemunt L, Li VS. A brief history of organoids. Am J Physiol Cell Physiol. 2020;319(1):C151-C165. 
  7. Moffett A. Organoid cultures as model systems to study disorders of the human endometrium and placenta. Obstetrics, Gynaecol Reprod Med. 2023;33(9):268-270.
  8. Alzamil L, Nikolakopoulou K, Turco MY. Organoid systems to study the human female reproductive tract and pregnancy. Cell Death Differ. 2021;28(1):35-51.
  9. Corsini NS, Knoblich JA. Human organoids: new strategies and methods for analyzing human development and disease. Cell. 2022;185(15):2756-2769.
  10. Stejskalova A, Vankelecom H, Sourouni M, Ho MY, Gotte M, Almquist BD. In vitro modelling of the physiological and diseased female reproductive system. Acta Biomater. 2021;132:288-312.
  11. Clevers H. Modeling development and disease with organoids. Cell. 2016;165(7):1586-1597.
  12. Li X, Li ZH, Wang YX, Liu TH. A comprehensive review of human trophoblast fusion models: recent developments and challenges. Cell Death Dis. 2023;9(1):372.
  13. De Vriendt S, Casares CM, Rocha S, Vankelecom H. Matrix scaffolds for endometrium-derived organoid models. Front Endocrinol (Lausanne). 2023;14:1240064.
  14. Nikolakopoulou K, Turco MY. Investigation of infertility using endometrial organoids. Reproduction. 2021;161(5):R113-R127.
  15. Park KW, Yang H, Wi H, Ock SA, Lee P, Hwang IS, et al. Effect of Wnt signaling pathway activation on the efficient generation of bovine intestinal organoids. J Anim Reprod Biotechnol. 2022;37(2):136-143.
  16. Hernandez-Gordillo V, Kassis T, Lampejo A, Choi G, Gamboa ME, Gnecco JS, et al. Fully synthetic matrices for in vitro culture of primary human intestinal enteroids and endometrial organoids. Biomaterials. 2020;254:120125.
  17. Fitzgerald HC, Dhakal P, Behura SK, Schust DJ, Spencer TE. Self-renewing endometrial epithelial organoids of the human uterus. Proc Natl Acad Sci U S A. 2019;116(46):23132-23142.
  18. Zhang Y, Zhao R, Yang C, Song J, Liu P, Li Y, et al. Human receptive endometrial organoid for deciphering the implantation window. eLife. 2023;12:RP90729.
  19. Luddi A, Pavone V, Semplici B, Governini L, Criscuoli M, Paccagnini E, et al. Organoids of human endometrium: a powerful in vitro model for the endometrium-embryo cross-talk at the implantation site. Cells. 2020;9(5):1121.
  20. Jamaluddin MF, Ghosh A, Ingle A, Mohammed R, Ali A, Bahrami M, et al. Bovine and human endometrium-derived hydrogels support organoid culture from healthy and cancerous tissues. Proc Natl Acad Sci U S A. 2022;119(44):e2208040119.
  21. Rawlings TM, Makwana K, Taylor DM, Mole MA, Fishwick KJ, Tryfonos M, et al. Modelling the impact of decidual senescence on embryo implantation in human endometrial assembloids. eLife. 2021;10:e69603.
  22. Zhou W, Barton S, Cui J, Santos LL, Yang G, Stern C, et al. Infertile human endometrial organoid apical protein secretions are dysregulated and impair trophoblast progenitor cell adhesion. Front Endocrinol (Lausanne). 2022;13:1067648.
  23. Frances-Herrero E, Juarez-Barber E, Campo H, Lopez-Martinez S, de Miguel-Gomez L, Faus A, et al. Improved models of human endometrial organoids based on hydrogels from decellularized endometrium. J Pers Med. 2021;11(6):504.
  24. Juarez-Barber E, Frances-Herrero E, Corachan A, Vidal C, Giles J, Alama P, et al. Establishment of adenomyosis organoids as a preclinical model to study infertility. J Pers Med. 2022;12(2):219. 
  25. Lalitkumar PG, Lalitkumar S, Meng CX, Stavreus-Evers A, Hambiliki F, Bentin-Ley U, et al. Mifepristone, but not levonorgestrel, inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model. Hum Reprod. 2007;22(11):3031-3037.
  26. Saadeldin IM, Han A, Bang S, Kang H, Kim H, Abady MM, et al. Generation of porcine endometrial organoids and their use as a model for enhancing embryonic attachment and elongation. Reproduction. 2023;167(2):e230429.
  27. Cindrova-Davies T, Zhao X, Elder K, Jones CJ, Moffett A, Burton GJ, et al. Menstrual flow as a non-invasive source of endometrial organoids. Commun Biol. 2021;4(1):651.
  28. Filby CE, Wyatt KA, Mortlock S, Cousins FL, McKinnon B, Tyson KE, et al. Comparison of organoids from menstrual fluid and hormone-treated endometrium: novel tools for gynecological research. J Pers Med. 2021;11(12):1314. 
  29. Burton GJ, Jauniaux E. What is the placenta? Am J Obstet Gynecol. 2015;213(4 Suppl):6.e1, S6-8.
  30. Turco MY, Gardner L, Kay RG, Hamilton RS, Prater M, Hollinshead MS, et al. Trophoblast organoids as a model for maternal-fetal interactions during human placentation. Nature. 2018;564(7735):263-267.
  31. Bacenkova D, Trebunova M, Cizkova D, Hudak R, Dosedla E, Findrik-Balogova A, et al. In vitro model of human trophoblast in early placentation. Biomedicines. 2022;10(4):904.
  32. Pascual F. Trophoblast organoids: a new tool for studying placental development. Environ Health Perspect. 2022;130(5):54003.
  33. Li Q, Turco MY, Moffett A. Trophoblast organoid systems to study human placentation. Dev Cell. 2024;59(6):693-694.
  34. Kim S, Cheng T, He S, Thiessen PA, Li Q, Gindulyte A, et al. PubChem protein, gene, pathway, and taxonomy data collections: bridging biology and chemistry through target-centric views of PubChem data. J Mol Biol. 2022;434(11):167514.
  35. Arutyunyan A, Roberts K, Troule K, Wong FC, Sheridan MA, Kats I, et al. Spatial multiomics map of trophoblast development in early pregnancy. Nature. 2023;616(7955):143-151.
  36. Sheridan MA, Fernando RC, Gardner L, Hollinshead MS, Burton GJ, Moffett A, et al. Establishment and differentiation of long-term trophoblast organoid cultures from the human placenta. Nat Protoc. 2020;15(10):3441-3463.
  37. van Rijn B, Van Opstal D, van Koetsveld N, Knapen M, Gribnau J, Schaffers O. Generation of trophoblast organoids from chorionic villus sampling. Organoids. 2024;3(1):54-66.
  38. Wallace AE, Fraser R, Cartwright JE. Extravillous trophoblast and decidual natural killer cells: a remodelling partnership. Hum Reprod Update. 2012;18(4):458-471.
  39. Hiby SE, Walker JJ, O'shaughnessy KM, Redman CW, Carrington M, Trowsdale J, et al. Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success. J Exp Med. 2004;200(8):957-965.
  40. Wu H, Huang XY, Sun MX, Wang Y, Zhou HY, Tian Y, et al. Zika virus targets human trophoblast stem cells and prevents syncytialization in placental trophoblast organoids. Nat Commun. 2023;14(1):5541.
  41. Horii M, Touma O, Bui T, Parast MM. Modeling human trophoblast, the placental epithelium at the maternal fetal interface. Reproduction. 2020;160(1):R1-R11.
  42. Kim Y, Kim I, Shin K. A new era of stem cell and developmental biology: from blastoids to synthetic embryos and beyond. Exp Mol Med. 2023;55(10):2127-2137.
  43. Pedroza M, Gassaloglu SI, Dias N, Zhong L, Hou TJ, Kretzmer H, et al. Self-patterning of human stem cells into post-implantation lineages. Nature. 2023;622(7983):574-583.
  44. Oura S, Hamilton JN, Wu J. Recent advances in stem cell-based blastocyst models. Curr Opin Genet Dev. 2023;81:102088.
  45. Vandana JJ, Manrique C, Lacko LA, Chen S. Human pluripotent-stem-cell-derived organoids for drug discovery and evaluation. Cell Stem Cell. 2023;30(5):571-591.
  46. Blasimme A, Sugarman J. Human stem cell-derived embryo models: Toward ethically appropriate regulations and policies. Cell Stem Cell. 2023;30(8):1008-1012.
  47. Rugg-Gunn PJ, Moris N, Tam PP. Technical challenges of studying early human development. Development. 2023;150(11):dev201797.
  48. Fu J, Warmflash A, Lutolf MP. Stem-cell-based embryo models for fundamental research and translation. Nat Mater. 2021;20(2):132-144.
  49. Luijkx D, Shankar V, van Blitterswijk C, Giselbrecht S, Vrij E. From mice to men: generation of human blastocyst-like structures in vitro. Front Cell Dev Biol. 2022;10:838356.
  50. Li R, Zhong C, Yu Y, Liu H, Sakurai M, Yu L, et al. Generation of blastocyst-like structures from mouse embryonic and adult cell cultures. Cell. 2019;179(3):687-702.e18.
  51. Oh SY, Na SB, Kang YK, Do JT. In vitro embryogenesis and gastrulation using stem cells in mice and humans. Int J Mol Sci. 2023;24(17):13655.
  52. Posfai E, Lanner F, Mulas C, Leitch HG. All models are wrong, but some are useful: establishing standards for stem cell-based embryo models. Stem Cell Reports. 2021;16(5):1117-1141.
  53. Blij S, Parenti A, Tabatabai-Yazdi N, Ralston A. Cdx2 efficiently induces trophoblast stem-like cells in naive, but not primed, pluripotent stem cells. Stem Cells Dev. 2015;24(11):1352-1365.
  54. Oldak B, Wildschutz E, Bondarenko V, Comar MY, Zhao C, Aguilera-Castrejon A, et al. Complete human day 14 post-implantation embryo models from naive ES cells. Nature. 2023;622(7983):562-573.
  55. Guo G, Stirparo GG, Strawbridge SE, Spindlow D, Yang J, Clarke J, et al. Human naive epiblast cells possess unrestricted lineage potential. Cell Stem Cell. 2021;28(6):1040-1056.e6.
  56. Brennan J, Lu CC, Norris DP, Rodriguez TA, Beddington RS, Robertson EJ. Nodal signalling in the epiblast patterns the early mouse embryo. Nature. 2001;411(6840):965-969.
  57. Hemberger M, Dean W. The placenta: epigenetic insights into trophoblast developmental models of a generation-bridging organ with long-lasting impact on lifelong health. Physiol Rev. 2023;103(4):2523-2560.
  58. Valenti MT, Serena M, Carbonare LD, Zipeto D. CRISPR/Cas system: An emerging technology in stem cell research. World J Stem Cells. 2019;11(11):937-956.
  59. Kobayashi N, Fu J. Stem cell-derived embryo models: a frontier of human embryology. Med Rev (2021). 2023;3(4):343-346.
  60. Semi K, Takashima Y. Pluripotent stem cells for the study of early human embryology. Dev Growth Differ. 2021;63(2):104-115.
  61. Weatherbee BA, Gantner CW, Iwamoto-Stohl LK, Daza RM, Hamazaki N, Shendure J, et al. Pluripotent stem cell-derived model of the post-implantation human embryo. Nature. 2023;622(7983):584-593.
  62. Tarazi S, Aguilera-Castrejon A, Joubran C, Ghanem N, Ashouokhi S, Roncato F, et al. Post-gastrulation synthetic embryos generated ex utero from mouse naive ESCs. Cell. 2022;185(18):3290-3306.e25.
  63. Amadei G, Handford CE, Qiu C, De Jonghe J, Greenfeld H, Tran M, et al. Embryo model completes gastrulation to neurulation and organogenesis. Nature. 2022;610(7930):143-153.
  64. Kagawa H, Javali A, Khoei HH, Sommer TM, Sestini G, Novatchkova M, et al. Human blastoids model blastocyst development and implantation. Nature. 2022;601(7894):600-605.
  65. Yu L, Wei Y, Duan J, Schmitz DA, Sakurai M, Wang L, et al. Blastocyst-like structures generated from human pluripotent stem cells. Nature. 2021;591(7851):620-626.
  66. Zheng Y, Xue X, Shao Y, Wang S, Esfahani SN, Li Z, et al. Controlled modelling of human epiblast and amnion development using stem cells. Nature. 2019;573(7774):421-425.
  67. Moris N, Anlas K, van den Brink SC, Alemany A, Schroder J, Ghimire S, et al. An in vitro model of early anteroposterior organization during human development. Nature. 2020;582(7812):410-415.
  68. Xu Y, Zhang T, Zhou Q, Hu M, Qi Y, Xue Y, et al. A single-cell transcriptome atlas profiles early organogenesis in human embryos. Nat Cell Biol. 2023;25(4):604-615.
  69. Gong Y, Bai B, Sun N, Ci B, Shao H, Zhang T, et al. Ex utero monkey embryogenesis from blastocyst to early organogenesis. Cell. 2023;186(10):2092-2110.e23.
  70. Zhai J, Xu Y, Wan H, Yan R, Guo J, Skory R, et al. Neurulation of the cynomolgus monkey embryo achieved from 3D blastocyst culture. Cell. 2023;186(10):2078-2091.e18.
  71. Li J, Zhu Q, Cao J, Liu Y, Lu Y, Sun Y, et al. Cynomolgus monkey embryo model captures gastrulation and early pregnancy. Cell Stem Cell. 2023;30(4):362-377.e7.
  72. Pham TX, Panda A, Kagawa H, To SK, Ertekin C, Georgolopoulos G, et al. Modeling human extraembryonic mesoderm cells using naive pluripotent stem cells. Cell Stem Cell. 2022;29(9):1346-1365.e10.
  73. Hadjantonakis AK, Siggia ED, Simunovic M. In vitro modeling of early mammalian embryogenesis. Curr Opin Biomed Eng. 2020;13:134-143.
  74. Paria BC, Ma W, Tan J, Raja S, Das SK, Dey SK, et al. Cellular and molecular responses of the uterus to embryo implantation can be elicited by locally applied growth factors. Proc Natl Acad Sci U S A. 2001;98(3):1047-1052.
  75. Robins JC, Morgan JR, Krueger P, Carson SA. Bioengineering anembryonic human trophoblast vesicles. Reprod Sci. 2011;18(2):128-135.
  76. Vrij EJ, Scholte op Reimer YS, Aldeguer JF, Guerreiro IM, Kind J, Koo BK, et al. Chemically-defined induction of a primitive endoderm and epiblast-like niche supports post-implantation progression from blastoids. bioRxiv. 2019 Apr 12. https://doi.org/10.1101/510396. 
  77. Christodoulou N, Weberling A, Strathdee D, Anderson KI, Timpson P, Zernicka-Goetz M. Morphogenesis of extra-embryonic tissues directs the remodelling of the mouse embryo at implantation. Nat Commun. 2019;10(1):3557. 
  78. Zheng X, Zhang L, Kuang Y, Venkataramani V, Jin F, Hein K, et al. Extracellular vesicles derived from neural progenitor cells--a preclinical evaluation for stroke treatment in mice. Transl Stroke Res. 2021;12(1):185-203.
  79. Yanez-Mo M, Siljander PR, Andreu Z, Zavec AB, Borras FE, Buzas EI, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4(1):27066.
  80. Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367(6478):eaau6977.
  81. Zhang Y, Liu Y, Liu H, Tang WH. Exosomes: biogenesis, biologic function and clinical potential. Cell Biosci. 2019;9(1):19.
  82. Vidal M. Exosomes: revisiting their role as "garbage bags". Traffic. 2019;20(11):815-828.
  83. Saadeldin IM, Tanga BM, Bang S, Fang X, Yoon KY, Lee S, et al. The theranostic roles of extracellular vesicles in pregnancy disorders. J Anim Reprod Biotechnol. 2022;37(1):2-12.
  84. Thompson RE, Bouma GJ, Hollinshead FK. The roles of extracellular vesicles and organoid models in female reproductive physiology. Int J Mol Sci. 2022;23(6):3186.
  85. Simintiras CA, Dhakal P, Ranjit C, Fitzgerald HC, Balboula AZ, Spencer TE. Capture and metabolomic analysis of the human endometrial epithelial organoid secretome. Proc Natl Acad Sci U S A. 2021;118(15):e2026804118.
  86. Juarez-Barber E, Segura-Benitez M, Carbajo-Garcia MC, Bas-Rivas A, Faus A, Vidal C, et al. Extracellular vesicles secreted by adenomyosis endometrial organoids contain miRNAs involved in embryo implantation and pregnancy. Reprod Biomed Online. 2023;46(3):470-481.
  87. Shao Y, Fu J. Engineering multiscale structural orders for high-fidelity embryoids and organoids. Cell Stem Cell. 2022;29(5):722-743.
  88. Murphy SV, Atala A. 3D bioprinting of tissues and organs. Nat Biotechnol. 2014;32(8):773-785.
  89. Hinton TJ, Jallerat Q, Palchesko RN, Park JH, Grodzicki MS, Shue HJ, et al. Three-dimensional printing of complex biological structures by freeform reversible embedding of suspended hydrogels. Sci Adv. 2015;1(9):e1500758.
  90. Rivron NC, Frias-Aldeguer J, Vrij EJ, Boisset JC, Korving J, Vivie J, et al. Blastocyst-like structures generated solely from stem cells. Nature. 2018;557(7703):106-111.
  91. Ren Y, Yang X, Ma Z, Sun X, Zhang Y, Li W, et al. Developments and opportunities for 3D bioprinted organoids. Int J Bioprint. 2021;7(3):364.
  92. Bhatia SN, Ingber DE. Microfluidic organs-on-chips. Nat Biotechnol. 2014;32(8):760-772.
  93. Sung JH, Yu J, Luo D, Shuler ML, March JC. Microscale 3-D hydrogel scaffold for biomimetic gastrointestinal (GI) tract model. Lab Chip. 2011;11(3):389-392.
  94. Bonner MG, Gudapati H, Mou X, Musah S. Microfluidic systems for modeling human development. Development. 2022;149(3):dev199463.
  95. Boretto M, Cox B, Noben M, Hendriks N, Fassbender A, Roose H, et al. Development of organoids from mouse and human endometrium showing endometrial epithelium physiology and long-term expandability. Development. 2017;144(10):1775-1786.
  96. Haider S, Meinhardt G, Saleh L, Kunihs V, Gamperl M, Kaindl U, et al. Self-renewing trophoblast organoids recapitulate the developmental program of the early human placenta. Stem Cell Reports. 2018;11(2):537-551.
  97. Yang L, Liang P, Yang H, Coyne CB. Trophoblast organoids with physiological polarity model placental structure and function. J Cell Sci. 2024;137(5):jcs261528.
  98. van Rijn B, Van Opstal D, van Koetsveld N, Knapen M, Gribnau J, Schaffers O. Generation of trophoblast organoids from chorionic villus sampling. Organoids. 2024;3(1):54-66.
  99. Hori T, Okae H, Shibata S, Kobayashi N, Kobayashi EH, Oike A, et al. Trophoblast stem cell-based organoid models of the human placental barrier. Nat Commun. 2024;15(1):962.
  100. De Santis R, Rice E, Croft G, Yang M, Rosado-Olivieri EA, Brivanlou AH. The emergence of human gastrulation upon in vitro attachment. Stem Cell Reports. 2024;19(1):41-53.