Heathman, TRJ;
Stolzing, A;
Fabian, C;
Rafiq, QA;
Coopman, K;
Nienow, AW;
Kara, B;
(2016)
Scalability and process transfer of mesenchymal stromal cell production from monolayer to microcarrier culture using human platelet lysate.
Cytotherapy
, 18
(4)
pp. 523-535.
10.1016/j.jcyt.2016.01.007.
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Abstract
BACKGROUND AIMS: The selection of medium and associated reagents for human mesenchymal stromal cell (hMSC) culture forms an integral part of manufacturing process development and must be suitable for multiple process scales and expansion technologies. METHODS: In this work, we have expanded BM-hMSCs in fetal bovine serum (FBS)- and human platelet lysate (HPL)-containing media in both a monolayer and a suspension-based microcarrier process. RESULTS: The introduction of HPL into the monolayer process increased the BM-hMSC growth rate at the first experimental passage by 0.049 day and 0.127/day for the two BM-hMSC donors compared with the FBS-based monolayer process. This increase in growth rate in HPL-containing medium was associated with an increase in the inter-donor consistency, with an inter-donor range of 0.406 cumulative population doublings after 18 days compared with 2.013 in FBS-containing medium. Identity and quality characteristics of the BM-hMSCs are also comparable between conditions in terms of colony-forming potential, osteogenic potential and expression of key genes during monolayer and post-harvest from microcarrier expansion. BM-hMSCs cultured on microcarriers in HPL-containing medium demonstrated a reduction in the initial lag phase for both BM-hMSC donors and an increased BM-hMSC yield after 6 days of culture to 1.20 ± 0.17 × 105 and 1.02 ± 0.005 × 105 cells/mL compared with 0.79 ± 0.05 × 105 and 0.36 ± 0.04 × 105 cells/mL in FBS-containing medium. CONCLUSIONS: This study has demonstrated that HPL, compared with FBS-containing medium, delivers increased growth and comparability across two BM-hMSC donors between monolayer and microcarrier culture, which will have key implications for process transfer during scale-up.
| Type: | Article |
|---|---|
| Title: | Scalability and process transfer of mesenchymal stromal cell production from monolayer to microcarrier culture using human platelet lysate |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jcyt.2016.01.007 |
| Publisher version: | https://doi.org/10.1016/j.jcyt.2016.01.007 |
| Language: | English |
| Additional information: | Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | bioprocess; cell-based therapy; comparability; harvest; human platelet lysate; manufacture; mesenchymal stromal cell; microcarrier expansion; process development; process transfer |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1557549 |
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