Qualitative and quantitative demonstration of bead-to-bead transfer with bone marrow-derived human mesenchymal stem cells on microcarriers: utilising the phenomenon to improve culture performance

Qasim A. Rafiq, Steven Ruck, Mariana P. Hanga, Thomas R.J. Heathman, Karen Coopman, Alvin W. Nienow, David J. Williams, Christopher Hewitt

Research output: Contribution to journalArticle

Abstract

Human mesenchymal stem cells (hMSCs) are a key candidate for advanced cell therapies with numerous clinical trials investigating their potential to treat acute and chronic indications. However, important translational and manufacturing challenges need to be addressed to improve our capability for scalable production of fully functional cells. In this study, we have demonstrated, both
qualitatively and quantitatively, the ability of bone marrow-derived hMSCs to migrate from one microcarrier to another, and, to populate fresh microcarriers when added into suspension culture. Additionally, we have shown that compared to inoculating a culture with cells in free suspension, inoculating 10% of near-confluent microcarriers from an initial seed microcarrier culture resulted in an increase in the cell growth rate and overall cell yield and a significant reduction in the lag phase.

These findings were consistent across cells from three different BM-hMSC donors and across different culture medium conditions, foetal bovine serum-supplemented medium, human platelet lysate-supplemented medium and serum-free medium. This new cells-on-beads inoculation method is an effective means of process intensification with the potential to decrease manufacturing times and potentially costs of hMSC-based therapies.
Original languageEnglish
Pages (from-to)11-21
JournalBiochemical Engineering Journal
Volume135
Early online date15 Nov 2017
DOIs
Publication statusPublished - 15 Jul 2018

Fingerprint

Stem cells
Mesenchymal Stromal Cells
Cell culture
Bone
Demonstrations
Bone Marrow
Suspensions
Cell- and Tissue-Based Therapy
Serum-Free Culture Media
Cell growth
Platelets
Culture Media
Blood Platelets
Cell Culture Techniques
Clinical Trials
Costs and Cost Analysis
Costs
Growth
Serum

Bibliographical note

© 2017, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International

Funding: Engineering and Physical Sciences Research Council via the E-TERM Landscape Fellowship programme (grant no. EP/I017801/1) and as part of the Doctoral Training Centre in Regenerative Medicine (grant no. EP/F500491/1), Bioprocessing Research Industry Club (BRIC) (grant No. BB/K011066/1 and BB/K01099/1) and Pall Life Sciences.

Keywords

  • human mesenchymal stem cells
  • cell therapy bioprocessing
  • microcarriers
  • bioreactor
  • regenerative medicine
  • bead to bead transfer
  • process intensification

Cite this

Rafiq, Qasim A. ; Ruck, Steven ; Hanga, Mariana P. ; Heathman, Thomas R.J. ; Coopman, Karen ; Nienow, Alvin W. ; Williams, David J. ; Hewitt, Christopher. / Qualitative and quantitative demonstration of bead-to-bead transfer with bone marrow-derived human mesenchymal stem cells on microcarriers : utilising the phenomenon to improve culture performance. In: Biochemical Engineering Journal. 2018 ; Vol. 135. pp. 11-21.
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Qualitative and quantitative demonstration of bead-to-bead transfer with bone marrow-derived human mesenchymal stem cells on microcarriers : utilising the phenomenon to improve culture performance. / Rafiq, Qasim A.; Ruck, Steven; Hanga, Mariana P.; Heathman, Thomas R.J.; Coopman, Karen; Nienow, Alvin W.; Williams, David J.; Hewitt, Christopher.

In: Biochemical Engineering Journal, Vol. 135, 15.07.2018, p. 11-21.

Research output: Contribution to journalArticle

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T2 - utilising the phenomenon to improve culture performance

AU - Rafiq, Qasim A.

AU - Ruck, Steven

AU - Hanga, Mariana P.

AU - Heathman, Thomas R.J.

AU - Coopman, Karen

AU - Nienow, Alvin W.

AU - Williams, David J.

AU - Hewitt, Christopher

N1 - © 2017, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Funding: Engineering and Physical Sciences Research Council via the E-TERM Landscape Fellowship programme (grant no. EP/I017801/1) and as part of the Doctoral Training Centre in Regenerative Medicine (grant no. EP/F500491/1), Bioprocessing Research Industry Club (BRIC) (grant No. BB/K011066/1 and BB/K01099/1) and Pall Life Sciences.

PY - 2018/7/15

Y1 - 2018/7/15

N2 - Human mesenchymal stem cells (hMSCs) are a key candidate for advanced cell therapies with numerous clinical trials investigating their potential to treat acute and chronic indications. However, important translational and manufacturing challenges need to be addressed to improve our capability for scalable production of fully functional cells. In this study, we have demonstrated, bothqualitatively and quantitatively, the ability of bone marrow-derived hMSCs to migrate from one microcarrier to another, and, to populate fresh microcarriers when added into suspension culture. Additionally, we have shown that compared to inoculating a culture with cells in free suspension, inoculating 10% of near-confluent microcarriers from an initial seed microcarrier culture resulted in an increase in the cell growth rate and overall cell yield and a significant reduction in the lag phase.These findings were consistent across cells from three different BM-hMSC donors and across different culture medium conditions, foetal bovine serum-supplemented medium, human platelet lysate-supplemented medium and serum-free medium. This new cells-on-beads inoculation method is an effective means of process intensification with the potential to decrease manufacturing times and potentially costs of hMSC-based therapies.

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