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Human cell-based models may aid in better treatment translation. We introduce 3D-UHU-TU, a bladder cancer microtissue model which incorporates spheroids derived from low- and high-grade human bladder cancer cell lines (RT112 and T24 respectively) into a healthy human urothelium.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>After model characterisation with histopathology and immunofluorescence microscopy, we trialled both the conventional chemotherapeutic Mitomycin C (MMC), and a novel herpes simplex oncolytic virus (oHSV-GFP), each assessed using confocal microscopy and cytotoxicity assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We observed correct expression of E- and N-Cadherin, CK7, CK20, GATA3 and Ki-67, alongside invasion and migration phenotypes. MMC treatment caused cell lysis and nuclear damage in cancer spheroids in both low- and high-grade models, with minimal damage to the surrounding healthy urothelium, and a significant increase in cleaved caspase 3 in low-grade models. oHSV-GFP co-localised in cancer spheroids and induced syncytia, spheroid disaggregation and cytotoxicity with minimal to no co-localisation or cytotoxicity in the healthy urothelium.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>3D-UHU-TU model is useful for testing both treatment safety and efficacy on different grades of bladder cancer. Future use of primary tumour spheroids in place of cell lines may allow a personalised medicine approach.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41416-026-03476-0","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T13:56:57Z","timestamp":1780408617000},"page":"697-707","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["An advanced in vitro bladder cancer model integrating bladder cancer spheroids into a healthy human urothelium for preclinical therapeutic testing"],"prefix":"10.1038","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9095-366X","authenticated-orcid":false,"given":"Benjamin O.","family":"Murray","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhui","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laia","family":"Pasquina-Lemonche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Swarbrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Simpson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Chambers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hardev","family":"Pandha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Freeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Rohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"3476_CR1","doi-asserted-by":"publisher","first-page":"351","DOI":"10.3233\/BLC-189035","volume":"4","author":"EM Messing","year":"2018","unstructured":"Messing EM. 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