The Microwell-mesh: A high-throughput 3D prostate cancer spheroid and drug-testing platform

  • Sci Rep. 2018 Jan 10;8(1):253. doi: 10.1038/s41598-017-18050-1.
E O Mosaad  1  2 ,  K F Chambers  3 ,  K Futrega  1 ,  J A Clements  4 ,  M R Doran  5  6  7  8
Affiliations
  • 1. Stem Cell Therapies Laboratory, Queensland University of Technology (QUT), Translational Research Institute (TRI), Brisbane, Australia.
  • 2. Biochemistry division, Chemistry Department, Faculty of Science, Damietta University, Damietta, Egypt.
  • 3. Quadram Institute Bioscience, Norwich Research Park, Norwich, UK.
  • 4. Australian Prostate Cancer Research Centre - Queensland (APCRC-Q), Brisbane, Australia.
  • 5. Stem Cell Therapies Laboratory, Queensland University of Technology (QUT), Translational Research Institute (TRI), Brisbane, Australia. [email protected].
  • 6. Australian Prostate Cancer Research Centre - Queensland (APCRC-Q), Brisbane, Australia. [email protected].
  • 7. Mater Research Institute - University of Queensland, Translational Research Institute (TRI), Brisbane, Australia. [email protected].
  • 8. Australian National Centre for the Public Awareness of Science, Australian National University, Canberra, Australia. [email protected].
PMID: 29321576 DOI: 10.1038/s41598-017-18050-1
Abstract

Treatment following early diagnosis of Prostate Cancer (PCa) is increasingly successful, whilst the treatment of advanced and metastatic PCa remains challenging. A major limitation in the development of new therapies is the prediction of drug efficacy using in vitro models. Classic in vitro 2-dimensional (2D) cell monolayer cultures are hypersensitive to anti-cancer drugs. As a result, there has been a surge in the development of platforms that enable three dimensional (3D) cultures thought to better replicate natural physiology and better predict drug efficacy. A deficiency associated with most 3D culture systems is that their complexity reduces the number of replicates and combination therapies that can be feasibly evaluated. Herein, we describe the use of a microwell platform that utilises a nylon mesh to retain 3D micro-tumours in discrete microwells; termed the Microwell-mesh. The Microwell-mesh enables the manufacture of ~150 micro-tumours per well in a 48-well plate, and response to anti-tumour drugs can be readily quantified. Our results demonstrate that 3D micro-tumours, unlike 2D monolayers, are not hypersensitive to Docetaxel or Abiraterone Acetate, providing a superior platform for the evaluation of sequential drug treatment. In summary, the Microwell-mesh provides an efficient 3D micro-tumour platform for single and sequential drug screening.

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