Heathman et al_Process Control Strategy_v5 04212018_and figures.pdf (1.01 MB)
Development of a process control strategy for the serum-free microcarrier expansion of human mesenchymal stem cells towards cost-effective and commercially viable manufacturing
journal contribution
posted on 2019-03-12, 08:46 authored by Thomas R.J. Heathman, Alvin W. Nienow, Qasim A. Rafiq, Karen CoopmanKaren Coopman, Bo Kara, Christopher J. HewittHuman Mesenchymal Stem Cells (hMSCs) are advancing through clinical development with the first allogeneic adult hMSC therapy receiving approval in Europe. To enable successful large-scale manufacture of hMSC therapies, increased product consistency and yield, and a reduced batch-to-batch variation must be achieved. This paper addresses ways to reduce variation by controlling the processing conditions, in particular the dissolved oxygen concentration (dO2), and the culture medium. Bone marrow derived hMSCs were cultured in DASGIP DASbox bioreactors on Plastic P-102L microcarriers in FBS-containing and serum free (SFM) media at various dO2 values from 100% to 10%, experiencing the same dO2 value throughout the culture process. The superior control of pH and dO2 in the bioreactor led to improved performances compared to poorly controlled spinner flasks, particularly at reduced dO2 concentrations. At 25% dO2, there was a 300% increase in the BM-hMSC yield in the bioreactor across the two donor BM-hMSCs in SFM compared to FBS-containing medium. Overall, the process yield increased by an average of around 500% for both donors under controlled conditions in SFM at 25% dO2 in the bioreactor compared to the poorly controlled expansion at atmospheric conditions in FBS-containing medium in spinner flasks. Process control significantly reduced the BM-hMSC variation in yield from 79.1% in FBS-containing medium in spinner flasks to <15% in controlled SFM bioreactor culture.
Funding
This study has been funded by the Engineering and Physical Sciences Research Council (EPSRC, EP/F500491/1) and FUJIFILM Diosynth Biotechnologies.
History
School
- Aeronautical, Automotive, Chemical and Materials Engineering
Department
- Chemical Engineering
Published in
Biochemical Engineering JournalVolume
141Pages
200 - 209Citation
HEATHMAN, T.R.J. ... et al, 2018. Development of a process control strategy for the serum-free microcarrier expansion of human mesenchymal stem cells towards cost-effective and commercially viable manufacturing. Biochemical Engineering Journal, 141, pp.200-209.Publisher
© ElsevierVersion
- AM (Accepted Manuscript)
Publisher statement
This paper was accepted for publication in the journal Biochemical Engineering Journal and the definitive published version is available at https://doi.org/10.1016/j.bej.2018.10.018Acceptance date
2018-10-16Publication date
2018-10-21Copyright date
2019ISSN
1369-703XPublisher version
Language
- en