Hollow Fibre Cancer Model for PK/PD

In a hollow fibre bioreactor an immortalised cell line will grow in 3 dimensions around porous, semi-permeable, protein-retentive “capillaries” that carry recirculating media on the luminal side. Cell densities in the available 3D space may go as high as 1E+8 cells/ml or more. These are conditions that resemble the in-vivo situation much more closely than monolayer cultured cells. Such cultures can be maintained continuously for long periods and cell division will typically be slower than in T-Flasks. Hollow fibres with a 20 kDa MWCO allow small molecules to freely equilibrate between the recirculating media and the cell compartment. This provides a basis of an in-vitro model that can be used to simulate any PK profile and to assess the effects of anti-tumour compounds over long periods of exposure. It is easy to make regular collections of cells and cell-conditioned media for analysis.

  • Simulate the PK concentration-time profiles of compounds
  • Collect samples at regular intervals to assess effects of compounds
  • Study the emergence of resistance over extended periods
  • Test combination regimens
  • Co-cultivation of different cell types
CHO cells growing in hollow fibre bioreactor

Both attachment-dependent or suspension cells can be cultured in a hollow fibre bioreactor. Once at high density, immortalized cells usually have the ability to continue growing independently of serum. Hollow fibres with molecular weight cut-offs of 5kDa and 20 kDa are available and also microporous fibres 0.1µm and 0.03µm.

HFIM set-up for antibiotic pk/pd

The FiberCell hollow fibre system is widely used as shown above to simulate human PK and represents a well referenced in-vitro infection model (HFIM) used, for example, to test antimicrobial regimens against M. tuberculosis. Learn more and see references here.

References:

Pharmacokinetic/Pharmacodynamic (PK/PD) Modeling of Anti-Neoplastic Agents: Daniel Lexcen, Ahmed Salem, Walid M. El-Khatib, Virginia Haynes and Ayman Noreddin (2012). [download chapter]

Pharmacodynamic characterization of gemcitabine cytotoxicity in an in vitro cell culture bioreactor system: Kirstein et al., Cancer Chemother Pharmacol (2007).[abstract]

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