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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Main Authors: Lydia Farrell, Cleo Bonnet, Alethea Tang, Severina Peneva, Non G. Williams, Sunil Dolwani, Lee Parry, Paul Dyson
Format: Article
Language:English
Published: MDPI AG 2025-04-01
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.
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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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