Characterization of an in vitro cell culture bioreactor system to evaluate anti-neoplastic drug regimens

Mark N. Kirstein, Richard C. Brundage, William F. Elmquist, Rory P. Remmel, Paul H. Marker, Dan E. Guire, Douglas Yee

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12 Scopus citations


A dynamic 3-dimensional tissue culture system has been developed that will allow for control of gemcitabine exposure to mimic concentration-time profiles measured from biologic samples. Gemcitabine was infused into a central reservoir. Media is mixed and delivered through hollow fiber capillaries, where it diffuses into the extracapillary space containing anchorage-dependent MDA-231 cells. To test for control of gemcitabine concentration-time profiles, drug was first infused through bioreactors without cells, and gemcitabine concentrations were measured with HPLC. Concentrations could be controlled to simulate 30-min and 2.5 h infusions, and were similar in both the lumen and extracapillary space. MDA-231 cells were then seeded into control (n = 4) and gemcitabine treatment (n = 4) groups, and maintained in culture for 2 weeks. Gemcitabine (5.3 mg) was infused over 30 min to the treatment group, and blank media to the control group. Accuracy of measured gemcitabine maximum concentration (C max) was 83.4%, and area under the curve (AUC), 106.2%, relative to pre-experimental theoretical values. With cells present, gemcitabine AUC in the extracapillary space was 32% of the value in the lumen. For the control group, 21.2 million cells (94.3% viable) were recovered, and for the gemcitabine-treated group, 16.8 million cells (87.1 % viable). Flow cytometry showed that 13.3 % of cells in the control group were in S-phase and 34.3 % in the gemcitabine-treated group were in S-phase (p = 0.003). In conclusion, gemcitabine concentration-time profiles could be accurately controlled through dosage, infusion rate, and pump flow rate, and cells could be recovered afterward to evaluate drug treatment.

Original languageEnglish (US)
Pages (from-to)217-225
Number of pages9
JournalBreast Cancer Research and Treatment
Issue number3
StatePublished - Apr 2006

Bibliographical note

Funding Information:
This work was supported in part by the Cancer Center Translational Breast Cancer Award to M.N.K.


  • Bioreactor
  • Gemcitabine
  • In vitro
  • MDA-231 cells
  • Pharmacokinetics
  • S-phase


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