Nutrient Regulation by Continuous Feeding Removes Limitations on Cell Yield in the Large-Scale Expansion of Mammalian Cell Spheroids

Bradley P. Weegman, Peter Nash, Alexandra L. Carlson, Kristin J. Voltzke, Zhaohui Geng, Marjan Jahani, Benjamin B. Becker, Klearchos K. Papas, Meri T. Firpo

Research output: Contribution to journalArticle

  • 2 Citations

Abstract

Cellular therapies are emerging as a standard approach for the treatment of several diseases. However, realizing the promise of cellular therapies across the full range of treatable disorders will require large-scale, controlled, reproducible culture methods. Bioreactor systems offer the scale-up and monitoring needed, but standard stirred bioreactor cultures do not allow for the real-time regulation of key nutrients in the medium. In this study, β-TC6 insulinoma cells were aggregated and cultured for 3 weeks as a model of manufacturing a mammalian cell product. Cell expansion rates and medium nutrient levels were compared in static, stirred suspension bioreactors (SSB), and continuously fed (CF) SSB. While SSB cultures facilitated increased culture volumes, no increase in cell yields were observed, partly due to limitations in key nutrients, which were consumed by the cultures between feedings, such as glucose. Even when glucose levels were increased to prevent depletion between feedings, dramatic fluctuations in glucose levels were observed. Continuous feeding eliminated fluctuations and improved cell expansion when compared with both static and SSB culture methods. Further improvements in growth rates were observed after adjusting the feed rate based on calculated nutrient depletion, which maintained physiological glucose levels for the duration of the expansion. Adjusting the feed rate in a continuous medium replacement system can maintain the consistent nutrient levels required for the large-scale application of many cell products. Continuously fed bioreactor systems combined with nutrient regulation can be used to improve the yield and reproducibility of mammalian cells for biological products and cellular therapies and will facilitate the translation of cell culture from the research lab to clinical applications.

Original languageEnglish (US)
Article numbere76611
JournalPLoS One
Volume8
Issue number10
DOIs
StatePublished - Oct 18 2013

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cells
Cephalothin
Bioreactors
Food
bioreactors
nutrients
Medieval History
Saimiriine herpesvirus 2
Glucose
glucose
Castration
therapeutics
Acromegaly
methodology
Aminoacridines
Iron Isotopes
Antimony Potassium Tartrate
Caprylates
Supravalvular Aortic Stenosis
Anthralin

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

MeSH PubMed subject areas

  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Nutrient Regulation by Continuous Feeding Removes Limitations on Cell Yield in the Large-Scale Expansion of Mammalian Cell Spheroids. / Weegman, Bradley P.; Nash, Peter; Carlson, Alexandra L.; Voltzke, Kristin J.; Geng, Zhaohui; Jahani, Marjan; Becker, Benjamin B.; Papas, Klearchos K.; Firpo, Meri T.

In: PLoS One, Vol. 8, No. 10, e76611, 18.10.2013.

Research output: Contribution to journalArticle

Weegman, Bradley P.; Nash, Peter; Carlson, Alexandra L.; Voltzke, Kristin J.; Geng, Zhaohui; Jahani, Marjan; Becker, Benjamin B.; Papas, Klearchos K.; Firpo, Meri T. / Nutrient Regulation by Continuous Feeding Removes Limitations on Cell Yield in the Large-Scale Expansion of Mammalian Cell Spheroids.

In: PLoS One, Vol. 8, No. 10, e76611, 18.10.2013.

Research output: Contribution to journalArticle

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