{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T16:03:32Z","timestamp":1789401812795,"version":"build-2803163510"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:p>The conventional cell culture models are not suitable for large-scale studies of genetic variation in disease mechanisms and drug response due to technical variability, high cost, and labor associated with them. Multiplex cell culture approaches, such as Village-in-a-Dish (ViaD), can address these limitations by enabling simultaneous studies of cells from many individuals in a single experiment. However, the multiplex design of ViaD poses several issues that differ from those of conventional cell culture. In this review, we identify and expound on the issues with ViaD and categorized them as platform-related (inherent to the design) or application-related (dependent on specific context or use). By providing a structured overview of these issues, our findings can help researchers incorporate key technical considerations during study design and interpretation and determine the context in which the multiplex cell culture approaches might be unsuitable.<\/jats:p>","DOI":"10.3389\/fbioe.2026.1923405","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T15:11:12Z","timestamp":1789398672000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Early considerations for village-in-a-dish platform: a multidisciplinary perspective"],"prefix":"10.3389","volume":"14","author":[{"given":"Talha","family":"Qureshi","sequence":"first","affiliation":[{"name":"Delft Centre for Entrepreneurship, Erasmus School of Health Policy and Management, Erasmus University Rotterdam","place":["Rotterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Bertocci","sequence":"additional","affiliation":[{"name":"Department Orthopaedics and Sports Medicine, Erasmus Medical Centre","place":["Rotterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Redekop","sequence":"additional","affiliation":[{"name":"Delft Centre for Entrepreneurship, Erasmus School of Health Policy and Management, Erasmus University Rotterdam","place":["Rotterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Vandekerckhove","sequence":"additional","affiliation":[{"name":"Delft Centre for Entrepreneurship, Erasmus School of Health Policy and Management, Erasmus University Rotterdam","place":["Rotterdam, Netherlands"]},{"name":"Delft Centre of Entrepreneurship, TU Delft","place":["Delft, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"IJzerman","sequence":"additional","affiliation":[{"name":"Delft Centre for Entrepreneurship, Erasmus School of Health Policy and Management, Erasmus University Rotterdam","place":["Rotterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"van Meurs","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Orthopaedics and Sports Medicine, Erasmus Medical Centre","place":["Rotterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carin Uyl-de","family":"Groot","sequence":"additional","affiliation":[{"name":"Delft Centre for Entrepreneurship, Erasmus School of Health Policy and Management, Erasmus University Rotterdam","place":["Rotterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Narcisi","sequence":"additional","affiliation":[{"name":"Department Orthopaedics and Sports Medicine, Erasmus Medical Centre","place":["Rotterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.immuni.2020.08.012","article-title":"Systemic immunometabolism: challenges and opportunities","volume":"53","author":"Alexander","year":"2020","journal-title":"Immunity"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1016\/j.cell.2017.05.038","article-title":"An expanded view of complex traits: from polygenic to omnigenic","volume":"169","author":"Boyle","year":"2017","journal-title":"Cell"},{"key":"B3","doi-asserted-by":"crossref","DOI":"10.1016\/j.stem.2020.06.004","volume-title":"A Multiplex Human Pluripotent Stem Cell Platform Defines Molecular and Functional Subclasses of autism-related Genes","author":"Cederquist","year":"2020"},{"key":"B4","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s13024-018-0258-4","article-title":"2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling","volume":"13","author":"Centeno","year":"2018","journal-title":"Mol. Neurodegener."},{"key":"B5","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s41392-024-01809-0","article-title":"Induced pluripotent stem cells (iPSCs): molecular mechanisms of induction and applications","volume":"9","author":"Cerneckis","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e5227","DOI":"10.21769\/BioProtoc.5227","article-title":"Human iPSC-derived neuron and oligodendrocyte co-culture as a small-molecule screening assay for myelination","volume":"15","author":"Chie","year":"2025","journal-title":"Bio-Protocol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1038\/s41467-020-14457-z","article-title":"Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression","volume":"11","author":"Cuomo","year":"2020","journal-title":"Nat. Commun."},{"key":"B8","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1038\/s41588-024-01731-9","article-title":"Integrating population genetics, stem cell biology and cellular genomics to study complex human diseases","volume":"56","author":"Farbehi","year":"2024","journal-title":"Nat. Genet."},{"key":"B9","doi-asserted-by":"publisher","first-page":"7301","DOI":"10.1038\/s41467-022-34940-z","article-title":"Greater genetic diversity is needed in human pluripotent stem cell models","volume":"13","author":"Ghosh","year":"2022","journal-title":"Nat. Commun."},{"key":"B10","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/s41576-019-0100-z","article-title":"Induced pluripotent stem cells in disease modelling and drug discovery","volume":"20","author":"Grant Rowe","year":"2019","journal-title":"Nat. Rev. Genet."},{"key":"B13","doi-asserted-by":"publisher","first-page":"12788","DOI":"10.1073\/pnas.1513533112","article-title":"CD8 T-cell recognition of acquired alloantigen promotes acute allograft rejection","volume":"112","author":"Harper","year":"2015","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1038\/s41588-021-00801-6","article-title":"Population-scale single-cell RNA-seq profiling across dopaminergic neuron differentiation","volume":"53","author":"Jerber","year":"2021","journal-title":"Nat. Genet."},{"key":"B16","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1038\/nature22403","article-title":"Common genetic variation drives molecular heterogeneity in human iPSCs","volume":"546","author":"Kilpinen","year":"2017","journal-title":"Nature"},{"key":"B17","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.jval.2016.12.010","article-title":"The HTA core Model\u00ae\u201410 years of developing an international framework to share multidimensional value assessment","volume":"20","author":"Kristensen","year":"2017","journal-title":"Value Health"},{"key":"B19","doi-asserted-by":"publisher","first-page":"5798","DOI":"10.1038\/s41598-020-62848-5","article-title":"Optimization of cell viability assays to improve replicability and reproducibility of cancer drug sensitivity screens","volume":"10","author":"Larsson","year":"2020","journal-title":"Sci. Rep."},{"key":"B21","doi-asserted-by":"publisher","first-page":"331","DOI":"10.2165\/11593380-000000000-00000","article-title":"Early assessment of medical technologies to inform product development and market access","volume":"9","author":"Maarten","year":"2011","journal-title":"Appl. Health Econ. Health Policy"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1320481","DOI":"10.3389\/fimmu.2023.1320481","article-title":"Characterization of CD4+ and CD8+ T cells responses in the mixed lymphocyte reaction by flow cytometry and single cell RNA sequencing","volume":"14","author":"Mangelinck","year":"2023","journal-title":"Front. Immunol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1056\/NEJM199510263331702","article-title":"Hepatic failure and lactic acidosis due to fialuridine (FIAU), an investigational nucleoside analogue for chronic hepatitis B","volume":"333","author":"McKenzie","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"B24","doi-asserted-by":"crossref","DOI":"10.1101\/2020.06.29.174383","volume-title":"Mapping Genetic Effects on Cellular Phenotypes with \u201cCell Villages\u201d","author":"Mitchell","year":"2020"},{"key":"B25","doi-asserted-by":"publisher","first-page":"3240","DOI":"10.1038\/s41467-023-38704-1","article-title":"A village in a dish model system for population-scale hiPSC studies","volume":"14","author":"Neavin","year":"2023","journal-title":"Nat. Commun."},{"key":"B26","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1017\/S0266462320000215","article-title":"The new definition of health technology assessment: a milestone in international collaboration","volume":"36","author":"O'Rourke","year":"2020","journal-title":"Int. J. Technol. Assess. Health Care"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1016\/j.stemcr.2017.03.012","article-title":"iPSCORE: a resource of 222 iPSC lines enabling functional characterization of genetic variation across a variety of cell types","volume":"8","author":"Panopoulos","year":"2017","journal-title":"Stem Cell Rep."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2038","DOI":"10.1038\/s41436-021-01248-0","article-title":"Disclosure of genetic information to family members: a systematic review of normative documents","volume":"23","author":"Phillips","year":"2021","journal-title":"Genet. Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"247","DOI":"10.3390\/pharmaceutics17020247","article-title":"Assessment of cell viability in drug therapy: IC50 and other new time-independent indices for evaluating chemotherapy efficacy","volume":"17","author":"S\u00e1nchez-D\u00edez","year":"2025","journal-title":"Pharmaceutics"},{"key":"B30","doi-asserted-by":"publisher","first-page":"118","DOI":"10.4252\/wjsc.v8.i4.118","article-title":"Human induced pluripotent stem cells for monogenic disease modelling and therapy","volume":"8","author":"Spitalieri","year":"2016","journal-title":"World J. Stem Cells"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"B32","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1038\/gim.2016.189","article-title":"Public variant databases: liability?","volume":"19","author":"Thorogood","year":"2017","journal-title":"Genet. Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"12606","DOI":"10.1038\/s41598-022-16896-8","article-title":"Human iPSC co-culture model to investigate the interaction between microglia and motor neurons","volume":"12","author":"Vahsen","year":"2022","journal-title":"Sci. Rep."},{"key":"B34","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1038\/s41431-026-02071-4","article-title":"Bridging population and cell: modelling complex diseases with human induced pluripotent stem cells","volume":"34","author":"van Zanten","year":"2026","journal-title":"Eur. J. Hum. Genet. EJHG"},{"key":"B35","doi-asserted-by":"publisher","first-page":"e13695","DOI":"10.1111\/cts.13695","article-title":"Complex in vitro model: a transformative model in drug development and precision medicine","volume":"17","author":"Wang","year":"2024","journal-title":"Clin. Transl. Sci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"682","DOI":"10.3390\/cells12050682","article-title":"A beginner\u2019s guide to cell culture: practical advice for preventing needless problems","volume":"12","author":"Weiskirchen","year":"2023","journal-title":"Cells"},{"key":"B37","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1016\/j.stem.2023.01.010","article-title":"Natural variation in gene expression and viral susceptibility revealed by neural progenitor cell villages","volume":"30","author":"Wells","year":"2023","journal-title":"Cell Stem Cell"},{"key":"B38","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/j.stem.2026.02.003","article-title":"Two decades of induced pluripotent stem cell research: from discovery to diverse applications","volume":"33","author":"Yamanaka","year":"2026","journal-title":"Cell Stem Cell"}],"container-title":["Frontiers in Bioengineering and Biotechnology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2026.1923405\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T15:11:13Z","timestamp":1789398673000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2026.1923405\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,14]]},"references-count":33,"alternative-id":["10.3389\/fbioe.2026.1923405"],"URL":"https:\/\/doi.org\/10.3389\/fbioe.2026.1923405","relation":{},"ISSN":["2296-4185"],"issn-type":[{"value":"2296-4185","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,14]]},"article-number":"1923405"}}