Mixing theory for culture and harvest in bioreactors of human mesenchymal stem cells on microcarriers

A.W. Nienow, Q.A. Rafiq, T.R.J. Heathman, K. Coopman, C.J. Hewitt

Research output: Contribution to journalArticlepeer-review

Abstract

The use of human mesenchymal stem cells (hMSCs) in regenerative medicine is a potential major advance for the treatment of many medical conditions, especially with the use of allogeneic therapies where the cells from a single donor can be used to treat ailments in many patients. Such cells must be grown attached to surfaces and for large scale production, it is shown that stirred bioreactors containing ~200 μm particles (microcarriers) can provide such a surface. It is also shown that the just suspended condition, agitator speed NJS, provides a satisfactory condition for cell growth by minimizing the specific energy dissipation rate, εT, in the bioreactor whilst still meeting the oxygen demand of the cells. For the cells to be used for therapeutic purposes, they must be detached from the microcarriers before being cryopreserved. A strategy based on a short period (~7 min) of very high εT, based on theories of secondary nucleation, is effective at removing >99% cells. Once removed, the cells are smaller than the Kolmogorov scale of turbulence and hence not damaged. This approach is shown to be successful for culture and detachment in 4 types of stirred bioreactors from 15 mL to 5 L.

Original languageEnglish
Pages (from-to)895-900
Number of pages6
JournalTheoretical Foundations of Chemical Engineering
Volume50
Issue number6
Early online date2 Dec 2016
DOIs
Publication statusE-pub ahead of print - 2 Dec 2016
Event15th European Conference on Mixing - St. Petersburg, Russian Federation
Duration: 25 Jan 20153 Jul 2015

Bibliographical note

The final publication is available at Springer via http://dx.doi.org/10.1134/S0040579516060117

Proceedings of XXV European Conference on Mixing “MIXING 15”

Funding: EPSRC, Lonza Cologne AG and FujiFilm Diosynth Biotechnologies.

Keywords

  • bioreactors
  • detachment
  • growth
  • mesenchymal stem cells
  • microcarriers
  • suspension

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