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

• Published in: Scientific reports Vol. 8; no. 1; p. 253
• Main Authors: Mosaad, E. O., Chambers, K. F., Futrega, K., Clements, J. A., Doran, M. R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.01.2018; Nature Publishing Group
• Subjects: 13; 13/1; 13/106; 13/107; 13/31; 14; 14/19; 14/63; 631/1647/767/70; 631/67/589/466; Acetic acid; Cell culture; Drug development; Drug screening; Humanities and Social Sciences; Metastases; multidisciplinary; Prostate cancer; Science; Science (multidisciplinary); Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-18050-1

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.