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Background <p>Despite therapy advances, better solutions for refractory bladder cancer remain an unmet need. 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.</p> Methods <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.</p> Results <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.</p> Conclusion <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.</p> <p></p>

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An advanced in vitro bladder cancer model integrating bladder cancer spheroids into a healthy human urothelium for preclinical therapeutic testing

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月2日

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  • Benjamin O. Murray,
  • Jinhui Gao,
  • Laia Pasquina-Lemonche,
  • Katherine Swarbrick,
  • Guy Simpson,
  • Mark A. Chambers,
  • Hardev Pandha,
  • Alex Freeman,
  • Jennifer L. Rohn

摘要

Background

Despite therapy advances, better solutions for refractory bladder cancer remain an unmet need. 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.

Methods

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.

Results

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.

Conclusion

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.