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A Novel 3D Polycaprolactone High-Throughput System for Evaluation of Toxicity in Normoxia and Hypoxia

Malakpour Permlid, Atena LU and Oredsson, Stina LU (2021) In Toxicology Reports 8. p.627-635
Abstract
Two-dimensional (2D) culturing of cancer cells has been indispensable for the development of anti-cancer drugs. Drug development, however, is lengthy and costly with a high attrition rate, calling to mind that 2D culturing does not mimic the three-dimensional (3D) tumour microenvironment in vivo. Thus, began the development of 3D culture models for cancer research. We have constructed a 3D 96-well plate using electrospun fibres made of biocompatible polycaprolactone (PCL). Finely-cut PCL fibre pieces in water/ethanol solution was pipetted to the wells of hydrophobic 96-well plates. A fibrous network of approximately 200 µm thickness and high porosity was formed after crosslinking and drying. Human JIMT-1 breast cancer cells and fibroblasts... (More)
Two-dimensional (2D) culturing of cancer cells has been indispensable for the development of anti-cancer drugs. Drug development, however, is lengthy and costly with a high attrition rate, calling to mind that 2D culturing does not mimic the three-dimensional (3D) tumour microenvironment in vivo. Thus, began the development of 3D culture models for cancer research. We have constructed a 3D 96-well plate using electrospun fibres made of biocompatible polycaprolactone (PCL). Finely-cut PCL fibre pieces in water/ethanol solution was pipetted to the wells of hydrophobic 96-well plates. A fibrous network of approximately 200 µm thickness and high porosity was formed after crosslinking and drying. Human JIMT-1 breast cancer cells and fibroblasts were seeded into the network. Confocal microscopy shows that the cells grow throughout the fibre network. The toxicity of paclitaxel and an experimental salinomycin analogue was assessed and compared in 2D and 3D cultures incubated under conditions of normoxia and hypoxia often found in tumours. The toxicity of both compounds is lower when the cells are cultured in 3D compared to 2D when cultured in either normoxia or hypoxia. We conclude that our 96-well assay is a cost-efficient tool that may be used for high-throughput pre-clinical screening of potential anti-cancer compounds. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Toxicology Reports
volume
8
pages
627 - 635
publisher
Elsevier
external identifiers
  • scopus:85103340255
  • pmid:33854950
ISSN
2214-7500
DOI
10.1016/j.toxrep.2021.03.015
language
English
LU publication?
yes
id
6e240289-9d6a-4059-8e54-24d293347d25
date added to LUP
2021-03-24 15:20:41
date last changed
2023-11-08 11:40:26
@article{6e240289-9d6a-4059-8e54-24d293347d25,
  abstract     = {{Two-dimensional (2D) culturing of cancer cells has been indispensable for the development of anti-cancer drugs. Drug development, however, is lengthy and costly with a high attrition rate, calling to mind that 2D culturing does not mimic the three-dimensional (3D) tumour microenvironment in vivo. Thus, began the development of 3D culture models for cancer research. We have constructed a 3D 96-well plate using electrospun fibres made of biocompatible polycaprolactone (PCL). Finely-cut PCL fibre pieces in water/ethanol solution was pipetted to the wells of hydrophobic 96-well plates. A fibrous network of approximately 200 µm thickness and high porosity was formed after crosslinking and drying. Human JIMT-1 breast cancer cells and fibroblasts were seeded into the network. Confocal microscopy shows that the cells grow throughout the fibre network. The toxicity of paclitaxel and an experimental salinomycin analogue was assessed and compared in 2D and 3D cultures incubated under conditions of normoxia and hypoxia often found in tumours. The toxicity of both compounds is lower when the cells are cultured in 3D compared to 2D when cultured in either normoxia or hypoxia. We conclude that our 96-well assay is a cost-efficient tool that may be used for high-throughput pre-clinical screening of potential anti-cancer compounds.}},
  author       = {{Malakpour Permlid, Atena and Oredsson, Stina}},
  issn         = {{2214-7500}},
  language     = {{eng}},
  month        = {{03}},
  pages        = {{627--635}},
  publisher    = {{Elsevier}},
  series       = {{Toxicology Reports}},
  title        = {{A Novel 3D Polycaprolactone High-Throughput System for Evaluation of Toxicity in Normoxia and Hypoxia}},
  url          = {{http://dx.doi.org/10.1016/j.toxrep.2021.03.015}},
  doi          = {{10.1016/j.toxrep.2021.03.015}},
  volume       = {{8}},
  year         = {{2021}},
}