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
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.
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]