Perfused three-dimensional organotypic culture of human cancer cells for therapeutic evaluation
Pharmaceutical research requires pre-clinical testing of new therapeutics using both in-vitro and in vivo models. However, the species specificity of non-human in-vivo models and the inadequate recapitulation of physiological conditions in-vitro are intrinsic weaknesses. Here we show that perfusion...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Published: |
Nature Publishing Group
2017
|
| _version_ | 1797062182493487104 |
|---|---|
| author | Wan, X Ball, S Willenbrock, F Yeh, S Vlahov, N Koennig, D Green, M Brown, G Jeyaretna, S Li, Z Cui, Z Ye, H O'Neill, E |
| author_facet | Wan, X Ball, S Willenbrock, F Yeh, S Vlahov, N Koennig, D Green, M Brown, G Jeyaretna, S Li, Z Cui, Z Ye, H O'Neill, E |
| author_sort | Wan, X |
| collection | OXFORD |
| description | Pharmaceutical research requires pre-clinical testing of new therapeutics using both in-vitro and in vivo models. However, the species specificity of non-human in-vivo models and the inadequate recapitulation of physiological conditions in-vitro are intrinsic weaknesses. Here we show that perfusion is a vital factor for engineered human tissues to recapitulate key aspects of the tumour microenvironment. Organotypic culture and human tumour explants were allowed to grow long-term (14-35 days) and phenotypic features of perfused microtumours compared with those in the static culture. Differentiation status and therapeutic responses were significantly different under perfusion, indicating a distinct biological response of cultures grown under static conditions. Furthermore, heterogeneous co-culture of tumour and endothelial cells demonstrated selective cell killing under therapeutic perfusion versus episodic delivery. We present a perfused 3D microtumour culture platform that sustains a more physiological tissue state and increased viability for long-term analyses. This system has the potential to tackle the disadvantages inherit of conventional pharmaceutical models and is suitable for precision medicine screening of tumour explants, particularly in hard-to-treat cancer types such as brain cancer which suffer from a lack of clinical samples. |
| first_indexed | 2024-03-06T20:41:55Z |
| format | Journal article |
| id | oxford-uuid:3492b912-584f-4f1d-a5b8-281f7ab7e636 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T20:41:55Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:3492b912-584f-4f1d-a5b8-281f7ab7e6362022-03-26T13:26:56ZPerfused three-dimensional organotypic culture of human cancer cells for therapeutic evaluationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3492b912-584f-4f1d-a5b8-281f7ab7e636Symplectic Elements at OxfordNature Publishing Group2017Wan, XBall, SWillenbrock, FYeh, SVlahov, NKoennig, DGreen, MBrown, GJeyaretna, SLi, ZCui, ZYe, HO'Neill, EPharmaceutical research requires pre-clinical testing of new therapeutics using both in-vitro and in vivo models. However, the species specificity of non-human in-vivo models and the inadequate recapitulation of physiological conditions in-vitro are intrinsic weaknesses. Here we show that perfusion is a vital factor for engineered human tissues to recapitulate key aspects of the tumour microenvironment. Organotypic culture and human tumour explants were allowed to grow long-term (14-35 days) and phenotypic features of perfused microtumours compared with those in the static culture. Differentiation status and therapeutic responses were significantly different under perfusion, indicating a distinct biological response of cultures grown under static conditions. Furthermore, heterogeneous co-culture of tumour and endothelial cells demonstrated selective cell killing under therapeutic perfusion versus episodic delivery. We present a perfused 3D microtumour culture platform that sustains a more physiological tissue state and increased viability for long-term analyses. This system has the potential to tackle the disadvantages inherit of conventional pharmaceutical models and is suitable for precision medicine screening of tumour explants, particularly in hard-to-treat cancer types such as brain cancer which suffer from a lack of clinical samples. |
| spellingShingle | Wan, X Ball, S Willenbrock, F Yeh, S Vlahov, N Koennig, D Green, M Brown, G Jeyaretna, S Li, Z Cui, Z Ye, H O'Neill, E Perfused three-dimensional organotypic culture of human cancer cells for therapeutic evaluation |
| title | Perfused three-dimensional organotypic culture of human cancer cells for therapeutic evaluation |
| title_full | Perfused three-dimensional organotypic culture of human cancer cells for therapeutic evaluation |
| title_fullStr | Perfused three-dimensional organotypic culture of human cancer cells for therapeutic evaluation |
| title_full_unstemmed | Perfused three-dimensional organotypic culture of human cancer cells for therapeutic evaluation |
| title_short | Perfused three-dimensional organotypic culture of human cancer cells for therapeutic evaluation |
| title_sort | perfused three dimensional organotypic culture of human cancer cells for therapeutic evaluation |
| work_keys_str_mv | AT wanx perfusedthreedimensionalorganotypiccultureofhumancancercellsfortherapeuticevaluation AT balls perfusedthreedimensionalorganotypiccultureofhumancancercellsfortherapeuticevaluation AT willenbrockf perfusedthreedimensionalorganotypiccultureofhumancancercellsfortherapeuticevaluation AT yehs perfusedthreedimensionalorganotypiccultureofhumancancercellsfortherapeuticevaluation AT vlahovn perfusedthreedimensionalorganotypiccultureofhumancancercellsfortherapeuticevaluation AT koennigd perfusedthreedimensionalorganotypiccultureofhumancancercellsfortherapeuticevaluation AT greenm perfusedthreedimensionalorganotypiccultureofhumancancercellsfortherapeuticevaluation AT browng perfusedthreedimensionalorganotypiccultureofhumancancercellsfortherapeuticevaluation AT jeyaretnas perfusedthreedimensionalorganotypiccultureofhumancancercellsfortherapeuticevaluation AT liz perfusedthreedimensionalorganotypiccultureofhumancancercellsfortherapeuticevaluation AT cuiz perfusedthreedimensionalorganotypiccultureofhumancancercellsfortherapeuticevaluation AT yeh perfusedthreedimensionalorganotypiccultureofhumancancercellsfortherapeuticevaluation AT oneille perfusedthreedimensionalorganotypiccultureofhumancancercellsfortherapeuticevaluation |