68. Carmelo JG, Fernandes-Platzgummer A, Diogo MM, da Silva CL, Cabral JMS (2015) A xenofree microcarrier-based stirred culture system for the scalable expansion of human mesenchymal stem/stromal cells isolated from bone marrow and adipose tissue. Biotechnol J
10:1235–1247. https://doi.org/10.1002/biot.201400586
69. Rafiq QA, Coopman K, Nienow AW, Hewitt CJ (2016) Systematic microcarrier screening and
agitated culture conditions improves human mesenchymal stem cell yield in bioreactors.
Biotechnol J 11:473–486. https://doi.org/10.1002/biot.201400862
70. Heathman TRJ, Stolzing A, Fabian C, Rafiq QA, Coopman K, Nienow AW, Kara B, Hewitt
CJ (2016) Scalability and process transfer of mesenchymal stromal cell production from
monolayer to microcarrier culture using human platelet lysate. Cytotherapy 18:523–535.
https://doi.org/10.1016/j.jcyt.2016.01.007
71. Nienow AW, Hewitt CJ, Heathman TRJ, Glyn VAM, Fonte GN, Hanga MP, Coopman K,
Rafiq QA (2016) Agitation conditions for the culture and detachment of hMSCs from
microcarriers in multiple bioreactor platforms. Biochem Eng J 108:24–29. https://doi.org/10.
1016/j.bej.2015.08.003
72. Dufey V, Tacheny A, Art M, Becken U, De Longueville F (2016) Expansion of human bone
marrow-derived mesenchymal stem cells in BioBLU 0.3c single-use bioreactors. Appl Note
305:1–8
73. Heathman TRJ, Nienow AW, Rafiq QA, Coopman K, Bo K, Hewitt CJ (2019) Development
of a process control strategy for the serum-free microcarrier expansion of human mesenchymal
stem cells towards cost-effective and commercially viable manufacturing. Biochem Eng J
141:200–209. https://doi.org/10.1016/j.bej.2018.10.018
74. Jossen V, Kaiser SC, Schirmaier C, Herrmann J, Tappe A, Eibl D, Siehoff A, van d BC, Eibl R
(2014) Modification and qualification of a stirred single-use bioreactor for the improved
expansion of human mesenchymal stem cells at benchtop scale. Pharm Bioprocess
2:311–322. https://doi.org/10.4155/pbp.14.29
75. Jossen V, Pörtner R, Kaiser SC, Kraume M, Eibl D, Eibl R (2014) Mass production of
mesenchymal stem cells – impact of bioreactor design and flow conditions on proliferation
and differentiation. In: Eberli D (ed) Cells and biomaterials in regenerative medicine. InTech,
Rijeka, pp 119–174
76. Siddiquee K, Sha M (2014) Large-scale production of human mesenchymal stem cells in
BioBLU 5c single-use vessels
77. Berry JD, Liovic P, Šutalo ID, Stewart RL, Glattauer V, Meagher L (2016) Characterisation of
stresses on microcarriers in a stirred bioreactor. App Math Model 40:6787–6804. https://doi.
org/10.1016/j.apm.2016.02.025
78. Paschedag AR (2004) CFD in der Vevfahrenstechnik. Wiley-VCH Verlag GmbH & Co.
79. Ferziger JH, Peric M, Leonard A (1997) Computational methods for fluid dynamics. Phys
Today 50:80–84. https://doi.org/10.1063/1.881751
80. Rodriguez S (2019) Applied computational fluid dynamics and turbulence modeling. Springer
International Publishing, Cham
81. Delafosse A, Collignon M-L, Marc A, Toye D, Olmos E (2015) Revisiting the determination
of hydromechanical stresses encountered by microcarriers in stem cell culture bioreactors.
BMC Proc 9:P41. https://doi.org/10.1186/1753-6561-9-S9-P41
82. Liovic P, Šutalo ID, Stewart R, Glattauer V, Meagher L (2012) Fluid flow and stresses on
microcarriers in spinner flask bioreactors. Ninth Int Conf CFD Miner Process Ind:1–6
83. Delafosse A, Calvo S, Collignon M-L, Delvigne F, Crine M, Toye D (2015) Euler–Lagrange
approach to model heterogeneities in stirred tank bioreactors – comparison to experimental
flow characterization and particle tracking. Chem Eng Sci 134:457–466. https://doi.org/10.
1016/j.ces.2015.05.045
84. Nienow AW, Rielly CD, Brosnan K, Bargh N, Lee K, Coopman K, Hewitt CJ (2013) The
physical characterisation of a microscale parallel bioreactor platform with an industrial CHO
cell line expressing an IgG4. Biochem Eng J 76:25–36. https://doi.org/10.1016/j.bej.2013.04.
011
226
V. Jossen et al.
10:1235–1247. https://doi.org/10.1002/biot.201400586
69. Rafiq QA, Coopman K, Nienow AW, Hewitt CJ (2016) Systematic microcarrier screening and
agitated culture conditions improves human mesenchymal stem cell yield in bioreactors.
Biotechnol J 11:473–486. https://doi.org/10.1002/biot.201400862
70. Heathman TRJ, Stolzing A, Fabian C, Rafiq QA, Coopman K, Nienow AW, Kara B, Hewitt
CJ (2016) Scalability and process transfer of mesenchymal stromal cell production from
monolayer to microcarrier culture using human platelet lysate. Cytotherapy 18:523–535.
https://doi.org/10.1016/j.jcyt.2016.01.007
71. Nienow AW, Hewitt CJ, Heathman TRJ, Glyn VAM, Fonte GN, Hanga MP, Coopman K,
Rafiq QA (2016) Agitation conditions for the culture and detachment of hMSCs from
microcarriers in multiple bioreactor platforms. Biochem Eng J 108:24–29. https://doi.org/10.
1016/j.bej.2015.08.003
72. Dufey V, Tacheny A, Art M, Becken U, De Longueville F (2016) Expansion of human bone
marrow-derived mesenchymal stem cells in BioBLU 0.3c single-use bioreactors. Appl Note
305:1–8
73. Heathman TRJ, Nienow AW, Rafiq QA, Coopman K, Bo K, Hewitt CJ (2019) Development
of a process control strategy for the serum-free microcarrier expansion of human mesenchymal
stem cells towards cost-effective and commercially viable manufacturing. Biochem Eng J
141:200–209. https://doi.org/10.1016/j.bej.2018.10.018
74. Jossen V, Kaiser SC, Schirmaier C, Herrmann J, Tappe A, Eibl D, Siehoff A, van d BC, Eibl R
(2014) Modification and qualification of a stirred single-use bioreactor for the improved
expansion of human mesenchymal stem cells at benchtop scale. Pharm Bioprocess
2:311–322. https://doi.org/10.4155/pbp.14.29
75. Jossen V, Pörtner R, Kaiser SC, Kraume M, Eibl D, Eibl R (2014) Mass production of
mesenchymal stem cells – impact of bioreactor design and flow conditions on proliferation
and differentiation. In: Eberli D (ed) Cells and biomaterials in regenerative medicine. InTech,
Rijeka, pp 119–174
76. Siddiquee K, Sha M (2014) Large-scale production of human mesenchymal stem cells in
BioBLU 5c single-use vessels
77. Berry JD, Liovic P, Šutalo ID, Stewart RL, Glattauer V, Meagher L (2016) Characterisation of
stresses on microcarriers in a stirred bioreactor. App Math Model 40:6787–6804. https://doi.
org/10.1016/j.apm.2016.02.025
78. Paschedag AR (2004) CFD in der Vevfahrenstechnik. Wiley-VCH Verlag GmbH & Co.
79. Ferziger JH, Peric M, Leonard A (1997) Computational methods for fluid dynamics. Phys
Today 50:80–84. https://doi.org/10.1063/1.881751
80. Rodriguez S (2019) Applied computational fluid dynamics and turbulence modeling. Springer
International Publishing, Cham
81. Delafosse A, Collignon M-L, Marc A, Toye D, Olmos E (2015) Revisiting the determination
of hydromechanical stresses encountered by microcarriers in stem cell culture bioreactors.
BMC Proc 9:P41. https://doi.org/10.1186/1753-6561-9-S9-P41
82. Liovic P, Šutalo ID, Stewart R, Glattauer V, Meagher L (2012) Fluid flow and stresses on
microcarriers in spinner flask bioreactors. Ninth Int Conf CFD Miner Process Ind:1–6
83. Delafosse A, Calvo S, Collignon M-L, Delvigne F, Crine M, Toye D (2015) Euler–Lagrange
approach to model heterogeneities in stirred tank bioreactors – comparison to experimental
flow characterization and particle tracking. Chem Eng Sci 134:457–466. https://doi.org/10.
1016/j.ces.2015.05.045
84. Nienow AW, Rielly CD, Brosnan K, Bargh N, Lee K, Coopman K, Hewitt CJ (2013) The
physical characterisation of a microscale parallel bioreactor platform with an industrial CHO
cell line expressing an IgG4. Biochem Eng J 76:25–36. https://doi.org/10.1016/j.bej.2013.04.
011
226
V. Jossen et al.