Organoids with a Type 1 Collagen Scaffold to Model Bacterial Cancer Therapy
Bacterial cancer therapy (BCT) is emerging as an important option for the treatment of solid tumours, with promising outcomes in preclinical trials. Further progress is hampered by an incomplete understanding of how oncotropic bacteria, such as attenuated strains of <i>Salmonella enterica</...
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| Format: | Article |
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MDPI AG
2025-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/14/7/524 |
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| author | Lydia Farrell Cleo Bonnet Alethea Tang Severina Peneva Non G. Williams Sunil Dolwani Lee Parry Paul Dyson |
| author_facet | Lydia Farrell Cleo Bonnet Alethea Tang Severina Peneva Non G. Williams Sunil Dolwani Lee Parry Paul Dyson |
| author_sort | Lydia Farrell |
| collection | DOAJ |
| description | Bacterial cancer therapy (BCT) is emerging as an important option for the treatment of solid tumours, with promising outcomes in preclinical trials. Further progress is hampered by an incomplete understanding of how oncotropic bacteria, such as attenuated strains of <i>Salmonella enterica</i> serovar Typhimurium, colonise tumours and the responses of both the bacteria and tumour cells to this colonisation. To model this, we developed organoids that are permissive for bacterial colonisation, replacing the conventional commercially available extracellular matrix (e.g., Matrigel) with a type I collagen matrix scaffold. A comparison of the two extracellular matrices indicated that type 1 collagen permitted an initial infection efficiency more than 5-times greater than with Matrigel. In addition, subsequent growth within type 1 collagen expanded bacterial cell numbers by over 10-fold within 4 days of infection. These organoids allow for the visualisation of bacterial chemoattraction, cell invasion and subsequent population of the interior lumen, and will permit the future optimisation of BCT. In addition, by establishing patient-derived organoids, we demonstrate a platform for developing future personalised treatments exploiting BCT. |
| format | Article |
| id | doaj-art-e88d37aaac3b46488f99093b41d5d51b |
| institution | DOAJ |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-e88d37aaac3b46488f99093b41d5d51b2025-08-20T03:06:27ZengMDPI AGCells2073-44092025-04-0114752410.3390/cells14070524Organoids with a Type 1 Collagen Scaffold to Model Bacterial Cancer TherapyLydia Farrell0Cleo Bonnet1Alethea Tang2Severina Peneva3Non G. Williams4Sunil Dolwani5Lee Parry6Paul Dyson7Institute of Life Science, Swansea University Medical School, Singleton Park, Swansea SA2 8PP, UKInstitute of Life Science, Swansea University Medical School, Singleton Park, Swansea SA2 8PP, UKInstitute of Life Science, Swansea University Medical School, Singleton Park, Swansea SA2 8PP, UKInstitute of Life Science, Swansea University Medical School, Singleton Park, Swansea SA2 8PP, UKEuropean Cancer Stem Cell Research Institute, School of Biosciences, Hadyn Ellis Building, Cardiff University, Maindy Road, Cardiff CF24 4HQ, UKSchool of Medicine, Cardiff University, Cardiff and Vale University Health Board, Cardiff CF14 4XN, UKEuropean Cancer Stem Cell Research Institute, School of Biosciences, Hadyn Ellis Building, Cardiff University, Maindy Road, Cardiff CF24 4HQ, UKInstitute of Life Science, Swansea University Medical School, Singleton Park, Swansea SA2 8PP, UKBacterial cancer therapy (BCT) is emerging as an important option for the treatment of solid tumours, with promising outcomes in preclinical trials. Further progress is hampered by an incomplete understanding of how oncotropic bacteria, such as attenuated strains of <i>Salmonella enterica</i> serovar Typhimurium, colonise tumours and the responses of both the bacteria and tumour cells to this colonisation. To model this, we developed organoids that are permissive for bacterial colonisation, replacing the conventional commercially available extracellular matrix (e.g., Matrigel) with a type I collagen matrix scaffold. A comparison of the two extracellular matrices indicated that type 1 collagen permitted an initial infection efficiency more than 5-times greater than with Matrigel. In addition, subsequent growth within type 1 collagen expanded bacterial cell numbers by over 10-fold within 4 days of infection. These organoids allow for the visualisation of bacterial chemoattraction, cell invasion and subsequent population of the interior lumen, and will permit the future optimisation of BCT. In addition, by establishing patient-derived organoids, we demonstrate a platform for developing future personalised treatments exploiting BCT.https://www.mdpi.com/2073-4409/14/7/524bacterial cancer therapyorganoid<i>Salmonella enterica</i> serovar Typhimuriumpersonalised medicinetype 1 collagen |
| spellingShingle | Lydia Farrell Cleo Bonnet Alethea Tang Severina Peneva Non G. Williams Sunil Dolwani Lee Parry Paul Dyson Organoids with a Type 1 Collagen Scaffold to Model Bacterial Cancer Therapy Cells bacterial cancer therapy organoid <i>Salmonella enterica</i> serovar Typhimurium personalised medicine type 1 collagen |
| title | Organoids with a Type 1 Collagen Scaffold to Model Bacterial Cancer Therapy |
| title_full | Organoids with a Type 1 Collagen Scaffold to Model Bacterial Cancer Therapy |
| title_fullStr | Organoids with a Type 1 Collagen Scaffold to Model Bacterial Cancer Therapy |
| title_full_unstemmed | Organoids with a Type 1 Collagen Scaffold to Model Bacterial Cancer Therapy |
| title_short | Organoids with a Type 1 Collagen Scaffold to Model Bacterial Cancer Therapy |
| title_sort | organoids with a type 1 collagen scaffold to model bacterial cancer therapy |
| topic | bacterial cancer therapy organoid <i>Salmonella enterica</i> serovar Typhimurium personalised medicine type 1 collagen |
| url | https://www.mdpi.com/2073-4409/14/7/524 |
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