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In this episode of Further Reading, we place assembloids in context — where the term came from, what these models enable beyond classical organoids, where they still fall short compared with explants, PDOs, and PDXs, and how they may evolve toward greater clinical relevance. We then situate these ideas in a recent human gastric multi‑regional assembloid study, showing how controlled assembly can drive epithelial maturation, functional parietal cell emergence, and acid secretion — and why this model choice makes sense for the questions being asked. Along the way, we take a brief devil’s‑advocate view: • What assembloids still lack (vasculature, immune complexity, systemic context) • What existing models still do better (PDE, PDO, PDX) • How vascularisation, immune integration, and multi‑organ systems could improve translational relevance This episode is designed for students, researchers, and clinicians who want to understand how to choose the right experimental model — and how to read these papers critically. The main paper discussed here: Jones BC, Benedetti G, Calà G, et al. Multi‑regional human gastric assembloids unlock functional parietal cell development and disease modelling. Nat Biomed Eng. 2026. Further References discussed in this video - Schmidt C. The rise of the assembloid. Nature. 2021;597(7878):S22–S23. doi:10.1038/d41586-021-02628-x. Birey F, Andersen J, Makinson CD, Islam S, Wei W, Huber N, et al. Assembly of functionally integrated human forebrain spheroids. Nature. 2017;545(7652):54–59. doi:10.1038/nature22330. Kanton S, Pașca SP. Human assembloids. Development. 2022;149(20):dev201120. doi:10.1242/dev.201120. Onesto MM, Kim JI, Pașca SP. Assembloid models of cell–cell interaction to study tissue and disease biology. Cell Stem Cell. 2024;31(11):1563–1573. doi:10.1016/j.stem.2024.10.003. Wu SR, Nowakowski TJ. Exploring human brain development and disease using assembloids. Neuron. 2025;113(8):1133–1150. doi:10.1016/j.neuron.2025.02.012. Pașca SP, Arlotta P, Bateup HS, Camp JG, Cappello S, Gage FH, et al. A framework for neural organoids, assembloids and transplantation studies. Nature. 2024. doi:10.1038/s41586-024-08487-6. Mei J, Liu X, Tian HX, Chen Y, Cao Y, Zeng J, et al. Tumour organoids and assembloids: patient‑derived cancer avatars for immunotherapy. Clin Transl Med. 2024;14:e1656. doi:10.1002/ctm2.1656. Kalla J, Pfneissl J, Mair T, Tran L, Egger G. A systematic review on the culture methods and applications of 3D tumoroids for cancer research and personalized medicine. Cell Oncol. 2025;48:1–26. doi:10.1007/s13402-024-00960-8. Polak R, Zhang ET, Kuo CJ. Cancer organoids 2.0: modelling the complexity of the tumour immune microenvironment. Nat Rev Cancer. 2024. doi:10.1038/s41568-024-00706-6. Ouaidat S, Bellapianta A, Ammer‑Pickhardt F, Taghipour T, Bolz M, Salti A. Exploring organoid and assembloid technologies: a focus on retina and brain. Expert Rev Mol Med. 2025;27:e14. doi:10.1017/erm.2025.9. 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. doi:10.7554/eLife.69603. Engevik AC, Kaji I, Goldenring JR. The physiology of the gastric parietal cell. Physiol Rev. 2020;100(2):573–602. doi:10.1152/physrev.00016.2019. Sahoo N, Gu M, Zhang X, Samuelson LC, Merchant JL, Xu H. Gastric acid secretion from parietal cells is mediated by a Ca2+ efflux channel in the tubulovesicle. Dev Cell. 2017;41(3):262–273.e6. doi:10.1016/j.devcel.2017.04.021. Nguyen NV, Gleeson PA, Courtois‑Coutry N, Caplan MJ, van Driel IR. Gastric parietal cell acid secretion can be regulated independently of H+/K+‑ATPase endocytosis. Gastroenterology. 2004;127(1):145–154. doi:10.1053/j.gastro.2004.04.006. Lancaster MA, Knoblich JA. Organogenesis in a dish: modeling development and disease using organoid technologies. Science. 2014;345(6194):1247125. doi:10.1126/science.1247125. 00:00 Intro & context 00:45 Figures – key results and interpretation 10:45 Paper craft – methodology in context 13:58 Paper craft - limitations 19:16 Summary & take-home messages