Systems for Cell Culture Scale‐Up

Halsall, Jennifer; Davis, John M.

doi:10.1002/9780470669815.ch10

Cited by 4 publications

(3 citation statements)

References 37 publications

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Section: Discussionmentioning

confidence: 99%

“…In addition to this, an agitated environment exposes the entirety of the microcarrier surface area to the cells, whereas static conditions do not. Indeed, one of the reasons to employ a microcarrier-based culture is to attain the benefits of a well-mixed, agitated system [21,44]. Whilst the difference between static and agitated conditions for microcarrier culture is significant, it is unlikely that a microcarrier-based process will ever be conducted under static conditions.…”

Section: Significant Improvement In Hbm-msc Yield In Agitated Culturementioning

confidence: 99%

See 1 more Smart Citation

Systematic microcarrier screening and agitated culture conditions improves human mesenchymal stem cell yield in bioreactors

Rafiq

Coopman

Nienow

et al. 2016

Biotechnology Journal

125

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Production of human mesenchymal stem cells for allogeneic cell therapies requires scalable, cost‐effective manufacturing processes. Microcarriers enable the culture of anchorage‐dependent cells in stirred‐tank bioreactors. However, no robust, transferable methodology for microcarrier selection exists, with studies providing little or no reason explaining why a microcarrier was employed. We systematically evaluated 13 microcarriers for human bone marrow‐derived MSC (hBM‐MSCs) expansion from three donors to establish a reproducible and transferable methodology for microcarrier selection. Monolayer studies demonstrated input cell line variability with respect to growth kinetics and metabolite flux. HBM‐MSC1 underwent more cumulative population doublings over three passages in comparison to hBM‐MSC2 and hBM‐MSC3. In 100 mL spinner flasks, agitated conditions were significantly better than static conditions, irrespective of donor, and relative microcarrier performance was identical where the same microcarriers outperformed others with respect to growth kinetics and metabolite flux. Relative growth kinetics between donor cells on the microcarriers were the same as the monolayer study. Plastic microcarriers were selected as the optimal microcarrier for hBM‐MSC expansion. HBM‐MSCs were successfully harvested and characterised, demonstrating hBM‐MSC immunophenotype and differentiation capacity. This approach provides a systematic method for microcarrier selection, and the findings identify potentially significant bioprocessing implications for microcarrier‐based allogeneic cell therapy manufacture.

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Section: Discussionmentioning

confidence: 99%

Section: Significant Improvement In Hbm-msc Yield In Agitated Culturementioning

confidence: 99%

Systematic microcarrier screening and agitated culture conditions improves human mesenchymal stem cell yield in bioreactors

Rafiq

Coopman

Nienow

et al. 2016

Biotechnology Journal

125

View full text Add to dashboard Cite

show abstract

“…Microcarriers are typically 100–450 µm in diameter and offers very large surface area per unit culture volume for cell attachment . However, the size distribution of microcarriers should be narrower because it is important for good mixing in a bioreactor, homogenous suspension of microcarriers, equal distribution of cells between microcarriers so that confluence of cells can be reached at about the same time on each microcarrier, and also for equal sedimentation during scale‐up steps in large‐scale processes . Given these reasons, an optimum balance is often achieved when the size of microcarriers is in the narrow 150–230 µm range, which is similar to many commercial microcarriers such as Cytodex (141–248 µm) and SoloHill (150–210 µm) microcarriers.…”

Section: Resultsmentioning

confidence: 99%