journal article Open Access Apr 27, 2025

An engineered human placental organoid microphysiological system in a vascular niche to model viral infection

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References
39
[1]
Knofler, M. et al. Human placenta and trophoblast development: key molecular mechanisms and model systems. Cell Mol. Life Sci. 76, 3479–3496 (2019). 10.1007/s00018-019-03104-6
[2]
Gude, N. M., Roberts, C. T., Kalionis, B. & King, R. G. Growth and function of the normal human placenta. Thromb. Res. 114, 397–407 (2004). 10.1016/j.thromres.2004.06.038
[3]
Kingdom, J., Huppertz, B., Seaward, G. & Kaufmann, P. Development of the placental villous tree and its consequences for fetal growth. Eur. J. Obstet. Gynecol. Reprod. Biol. 92, 35–43 (2000). 10.1016/s0301-2115(00)00423-1
[4]
Hamilton, W. J. & Boyd, J. D. Development of the human placenta in the first three months of gestation. J. Anat. 94, 297–328 (1960).
[5]
Sato, Y. Endovascular trophoblast and spiral artery remodeling. Mol. Cell Endocrinol. 503, 110699 (2020). 10.1016/j.mce.2019.110699
[6]
Moll, W. Structure adaptation and blood flow control in the uterine arterial system after hemochorial placentation. Eur. J. Obstet. Gynecol. Reprod. Biol. 110, S19–S27 (2003). Suppl 1. 10.1016/s0301-2115(03)00169-6
[7]
Soares, M. J., Varberg, K. M. & Iqbal, K. Hemochorial placentation: development, function, and adaptations. Biol. Reprod. 99, 196–211 (2018). 10.1093/biolre/ioy049
[8]
Ander, S. E., Diamond, M. S. & Coyne, C. B. Immune responses at the maternal-fetal interface. Sci. Immunol. 4, eaat6117 (2019). 10.1126/sciimmunol.aat6114
[9]
Pereira, L. Congenital viral infection: traversing the uterine-placental interface. Annu. Rev. Virol. 5, 273–299 (2018). 10.1146/annurev-virology-092917-043236
[10]
Rosenfeld, C. S. Transcriptomics and other omics approaches to investigate effects of xenobiotics on the placenta. Front Cell Dev. Biol. 9, 723656 (2021). 10.3389/fcell.2021.723656
[11]
Bayer, A. et al. Type III interferons produced by human placental trophoblasts confer protection against Zika virus infection. Cell Host Microbe 19, 705–712 (2016). 10.1016/j.chom.2016.03.008
[12]
Corry, J., Arora, N., Good, C. A., Sadovsky, Y. & Coyne, C. B. Organotypic models of type III interferon-mediated protection from Zika virus infections at the maternal-fetal interface. Proc. Natl Acad. Sci. USA 114, 9433–9438 (2017). 10.1073/pnas.1707513114
[13]
Lazear, H. M., Schoggins, J. W. & Diamond, M. S. Shared and distinct functions of type I and type III interferons. Immunity 50, 907–923 (2019). 10.1016/j.immuni.2019.03.025
[14]
Roberts, R. M., Green, J. A. & Schulz, L. C. The evolution of the placenta. Reproduction 152, R179–R189 (2016). 10.1530/rep-16-0325
[15]
Maltepe, E., Bakardjiev, A. I. & Fisher, S. J. The placenta: transcriptional, epigenetic, and physiological integration during development. J. Clin. Invest. 120, 1016–1025 (2010). 10.1172/jci41211
[16]
Cui, K. et al. Establishment of trophoblast-like tissue model from human pluripotent stem cells in three-dimensional culture system. Adv. Sci. 9, 2100031 (2021). 10.1002/advs.202100031
[17]
Deng, P. et al. Fluidic flow enhances the differentiation of placental trophoblast-like 3D tissue from hiPSCs in a perfused macrofluidic device. Front. Bioeng. Biotechnol. 10, 907104 (2022). 10.3389/fbioe.2022.907104
[18]
Haider, S. et al. Self-renewing trophoblast organoids recapitulate the developmental program of the early human placenta. Stem Cell Rep. 11, 537–551 (2018). 10.1016/j.stemcr.2018.07.004
[19]
Turco, M. Y. et al. Trophoblast organoids as a model for maternal-fetal interactions during human placentation. Nature 564, 263–267 (2018). 10.1038/s41586-018-0753-3
[20]
Takebe, T., Zhang, B. & Radisic, M. Synergistic engineering: organoids meet organs-on-a-chip. Cell Stem Cell 21, 297–300 (2017). 10.1016/j.stem.2017.08.016
[21]
Zhu, Y. et al. In situ generation of human brain organoids on a micropillar array. Lab Chip 17, 2941–2950 (2017). 10.1039/c7lc00682a
[22]
Wang, Y., Wang, L., Zhu, Y. & Qin, J. Human brain organoid-on-a-chip to model prenatal nicotine exposure. Lab chip 18, 851–860 (2018). 10.1039/c7lc01084b
[23]
Park, S. E., Georgescu, A. & Huh, D. Organoids-on-a-chip. Science 364, 960–965 (2019). 10.1126/science.aaw7894
[24]
Turco, M. Y. & Moffett, A. Development of the human placenta. Development 146 (2019). 10.1242/dev.163428
[25]
Battegay, E. J., Rupp, J., Iruela-Arispe, L., Sage, E. H. & Pech, M. PDGF-BB modulates endothelial proliferation and angiogenesis in vitro via PDGF beta-receptors. J. Cell Biol. 125, 917–928 (1994). 10.1083/jcb.125.4.917
[26]
Megli, C., Morosky, S., Rajasundaram, D. & Coyne, C. B. Inflammasome signaling in human placental trophoblasts regulates immune defense against Listeria monocytogenes infection. J. Exp. Med. 218, e20200649 (2021). 10.1084/jem.20200649
[27]
Ma, H. et al. Conditioned medium from primary cytotrophoblasts, primary placenta-derived mesenchymal stem cells, or sub-cultured placental tissue promoted HUVEC angiogenesis in vitro. Stem Cell Res. Ther. 12, 141 (2021). 10.1186/s13287-021-02192-1
[28]
Ghosh Roy, S. TAM receptors: a phosphatidylserine receptor family and its implications in viral infections. Int Rev. Cell Mol. Biol. 357, 81–122 (2020). 10.1016/bs.ircmb.2020.09.003
[29]
Wang, Y. Q. et al. In situ differentiation and generation of functional liver organoids from human iPSCs in a 3D perfusable chip system. Lab a chip 18, 3606–3616 (2018). 10.1039/c8lc00869h
[30]
Wang, Y. Q., Wang, L., Guo, Y. Q., Zhu, Y. J. & Qin, J. H. Engineering stem cell-derived 3D brain organoids in a perfusable organ-on-a-chip system. RSC Adv. 8, 1677–1685 (2018). 10.1039/c7ra11714k
[31]
Sang, Q. X. Complex role of matrix metalloproteinases in angiogenesis. Cell Res. 8, 171–177 (1998). 10.1038/cr.1998.17
[32]
Guleria, I. & Pollard, J. W. The trophoblast is a component of the innate immune system during pregnancy. Nat. Med. 6, 589–593 (2000). 10.1038/75074
[33]
Popovici, R. M. et al. Gene expression profiling of human endometrial-trophoblast interaction in a coculture model. Endocrinology 147, 5662–5675 (2006). 10.1210/en.2006-0916
[34]
Sheridan, M. A. et al. Vulnerability of primitive human placental trophoblast to Zika virus. Proc. Natl Acad. Sci. USA 114, E1587–E1596 (2017). 10.1073/pnas.1616097114
[35]
Zika virus targets human trophoblast stem cells and prevents syncytialization in placental trophoblast organoids

Hao Wu, Xing-Yao Huang, Meng-Xu Sun et al.

Nature Communications 2023 10.1038/s41467-023-41158-0
[36]
Tabata, T. et al. Virus targets different primary human placental cells, suggesting two routes for vertical transmission. Cell Host Microbe 20, 155–166 (2016). 10.1016/j.chom.2016.07.002
[37]
Xiang, L. et al. A developmental landscape of 3D-cultured human pre-gastrulation embryos. Nature 577, 537–542 (2020). 10.1038/s41586-019-1875-y
[38]
Cao, R., Wang, Y., Liu, J., Rong, L. & Qin, J. Self-assembled human placental model from trophoblast stem cells in a dynamic organ-on-a-chip system. Cell Prolif. 56, e13469 (2023). 10.1111/cpr.13469
[39]
Derivation of Human Trophoblast Stem Cells

Hiroaki Okae, Hidehiro Toh, Tetsuya Sato et al.

Cell Stem Cell 2018 10.1016/j.stem.2017.11.004
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