TY - JOUR
T1 - Qualitative and quantitative demonstration of bead-to-bead transfer with bone marrow-derived human mesenchymal stem cells on microcarriers:
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 J.
PY - 2017/11/15
Y1 - 2017/11/15
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, 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.
AB - 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.
KW - human mesenchymal stem cells
KW - cell therapy bioprocessing
KW - microcarriers
KW - bioreactor
KW - regenerative medicine
KW - bead to bead transfer
KW - process intensification
U2 - 10.1016/j.bej.2017.11.005
DO - 10.1016/j.bej.2017.11.005
M3 - Article
SN - 1369-703X
JO - Biochemical Engineering Journal
JF - Biochemical Engineering Journal
ER -