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|Title: ||Characterisation of human mesenchymal stem cells from multiple donors and the implications for large scale bioprocess development|
|Authors: ||Heathman, Thomas R.J.|
Rafiq, Qasim A.
Chan, Alexander K.C.
Nienow, Alvin W.
Hewitt, Christopher J.
|Keywords: ||Bioprocess design|
Tissue cell culture
Human mesenchymal stem cells
|Issue Date: ||2016|
|Publisher: ||© The Authors. Published by Elsevier B.V.|
|Citation: ||HEATHMAN, T.R.J. et al., 2016. Characterisation of human mesenchymal stem cells from multiple donors and the implications for large scale bioprocess development. Biochemical Engineering Journal, 108, pp.14-23.|
|Abstract: ||Cell-based therapies have the potential to contribute to global healthcare, whereby the use of living cells
and tissues can be used as medicinal therapies. Despite this potential, many challenges remain before the
full value of this emerging field can be realized. The characterization of input material for cell-based therapy
bioprocesses from multiple donors is necessary to identify and understand the potential implications
of input variation on process development. In this work, we have characterized bone marrow derived
human mesenchymal stem cells (BM-hMSCs) from multiple donors and discussed the implications of
the measurable input variation on the development of autologous and allogeneic cell-based therapy
manufacturing processes. The range of cumulative population doublings across the five BM-hMSC lines
over 30 days of culture was 5.93, with an 18.2% range in colony forming efficiency at the end of the
culture process and a 55.1% difference in the production of interleukin-6 between these cell lines. It has
been demonstrated that this variation results in a range in the process time between these donor hMSC
lines for a hypothetical product of over 13 days, creating potential batch timing issues when manufacturing
products from multiple patients. All BM-hMSC donor lines demonstrated conformity to the ISCT
criteria but showed a difference in cell morphology. Metabolite analysis showed that hMSCs from the
different donors have a range in glucose consumption of 26.98 pmol cell−1 day−1, Lactate production of
29.45 pmol cell−1 day−1 and ammonium production of 1.35 pmol cell−1 day−1, demonstrating the extent
of donor variability throughout the expansion process. Measuring informative product attributes during
process development will facilitate progress towards consistent manufacturing processes, a critical step
in the translation cell-based therapies.|
|Description: ||This is an open access article published by Elsevier under the CC BY license
|Sponsor: ||Engineering and Physical
Sciences Research Council (EPSRC) [grant number: EP/F500491/1], FUJIFILM Diosynth Biotechnologies,
Lonza Cologne AG and Loughborough University|
|Publisher Link: ||http://dx.doi.org/10.1016/j.bej.2015.06.018|
|Appears in Collections:||Published Articles (Chemical Engineering)|
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