Bioreactor; Light attenuation technique; Microcarrier; Suspension; Agitation rates; Distribution of particles; Light attenuation; Mesenchymal stromal cells; Microcarriers; Particles concentration; Particles suspension; Re-suspension; Temporal evolution; Chemistry (all); Chemical Engineering (all); Industrial and Manufacturing Engineering
Abstract :
[en] The culture of mesenchymal stromal cells relies on the use of suspended microcarriers as adhesion supports. During the particle suspension phases, the temporal evolution of the spatial distribution of particle concentrations is generally poorly characterized. In this study, the light attenuation technique was used to access this distribution and the duration of particle homogenization. Considering the minimal agitation rate Nref for which particle suspension was observed for all the microcarrier concentrations 〈C〉 studied, the results showed that using an agitation frequency close to Nref significantly increased the homogenization duration compared to N≃1.7×Nref. The transient microcarrier overconcentration was also determined locally. At N=Nref, the resuspension time was negatively impacted by 〈C〉, which also resulted in longer particle overconcentrations. A time-integral particle overconcentration term was considered to estimate the severity of inter-microcarrier collisions. The results suggested that increased agitation could limit time-cumulative overconcentrations beyond a particle concentration of 3 g/L.
Disciplines :
Chemical engineering Biotechnology
Author, co-author :
Maillot, Charlotte; Université de Lorraine, CNRS, LRGP, Nancy, France
Delafosse, Angélique ; Université de Liège - ULiège > Department of Chemical Engineering > PEPs - Products, Environment, and Processes
De Isla, Natalia; Ingénierie Moléculaire et Physiopathologie Articulaire, Université de Lorraine, CNRS UMR 7365, Vandoeuvre-lès-Nancy, France
Olmos, Eric ; Université de Lorraine, CNRS, LRGP, Nancy, France
Toye, Dominique ; Université de Liège - ULiège > Department of Chemical Engineering > PEPs - Products, Environment, and Processes
Language :
English
Title :
Experimental study of transient particle suspension in bioreactors using a light attenuation technique
Ascanio, G., Mixing time in stirred vessels: a review of experimental techniques. Chin. J. Chem. Eng. 23 (2015), 1065–1076.
Berry, J., Liovic, P., Šutalo, I., Stewart, R., Glattauer, V., Meagher, L., Characterisation of stresses on microcarriers in a stirred bioreactor. Appl. Math. Model. 40 (2016), 6787–6804.
Cherry, R.S., Papoutsakis, E.T., Physical mechanisms of cell damage in microcarrier cell culture bioreactors. Biotechnol. Bioeng. 32 (1988), 1001–1014.
Collignon, M.L., Delafosse, A., Calvo, S., Martin, C., Marc, A., Toye, D., Olmos, E., Large-eddy simulations of microcarrier exposure to potentially damaging eddies inside mini-bioreactors. Biochem. Eng. J. 108 (2016), 30–43.
Delafosse, A., Loubière, C., Calvo, S., Toye, D., Olmos, E., Solid-liquid suspension of microcarriers in stirred tank bioreactor – experimental and numerical analysis. Chem. Eng. Sci. 180 (2018), 52–63.
Discher, D.E., Janmey, P., Wang, Y.L., Tissue cells feel and respond to the stiffness of their substrate. Science 310 (2005), 1139–1143.
Ferrari, C., Balandras, F., Guedon, E., Olmos, E., Chevalot, I., Marc, A., Limiting cell aggregation during mesenchymal stem cell expansion on microcarriers. Biotechnol. Prog. 28 (2012), 780–787.
Grangier, A., Wilhelm, C., Gazeau, F., Silva, A., High yield and scalable ev production from suspension cells triggered by turbulence in a bioreactor. Cytotherapy, 22, 2020, S50.
Grein, T.A., Leber, J., Blumenstock, M., Petry, F., Weidner, T., Salzig, D., Czermak, P., Multiphase mixing characteristics in a microcarrier-based stirred tank bioreactor suitable for human mesenchymal stem cell expansion. Process Biochem. 51 (2016), 1109–1119.
Harburger, D.S., Calderwood, D.A., Integrin signalling at a glance. J. Cell Sci. 122 (2009), 159–163.
Ibrahim, S., Nienow, A., Suspension of microcarriers for cell culture with axial flow impellers. Chem. Eng. Res. Des. 82 (2004), 1082–1088.
Jossen, V., Schirmer, C., Mostafa Sindi, D., Eibl, R., Kraume, M., Pörtner, R., Eibl, D., et al. Theoretical and practical issues that are relevant when scaling up hmsc microcarrier production processes. Stem Cells Int., 2016, 2016.
Kawase, Y., Moo-Young, M., Mathematical models for design of bioreactors: applications of: Kolmogoroff's theory of isotropic turbulence. Chem. Eng. J. 43 (1990), B19–B41.
Maillot, C., Quantification and impact of microcarrier collisions during mesenchymal stem cell culture in bioreactors. Ph.D. thesis, 2022, University of Lorraine, France.
Maillot, C., De Isla, N., Loubiere, C., Toye, D., Olmos, E., Impact of microcarrier concentration on mesenchymal stem cell growth and death: experiments and modeling. Biotechnol. Bioeng. 119 (2022), 3537–3548.
Maillot, C., Sion, C., De Isla, N., Toye, D., Olmos, E., Quality by design to define critical process parameters for mesenchymal stem cell expansion. Biotechnol. Adv., 50, 2021, 107765.
Nienow, A., Coopman, K., Heathman, T., Rafiq, Q., Hewitt, C., Bioreactor engineering fundamentals for stem cell manufacturing. Stem Cell Manufacturing, 2016, Elsevier, 43–75.
Nienow, A.W., Hewitt, C.J., Heathman, T.R., Glyn, V.A., Fonte, G.N., Hanga, M.P., Coopman, K., Rafiq, Q.A., Agitation conditions for the culture and detachment of hmscs from microcarriers in multiple bioreactor platforms. Biochem. Eng. J. 108 (2016), 24–29.
Nienow, A.W., Rafiq, Q.A., Coopman, K., Hewitt, C.J., A potentially scalable method for the harvesting of hmscs from microcarriers. Biochem. Eng. J. 85 (2014), 79–88.
Papoutsakis, E.T., Fluid-mechanical damage of animal cells in bioreactors. Trends Biotechnol. 9 (1991), 427–437.
Piffoux, M., Nicolás-Boluda, A., Mulens-Arias, V., Richard, S., Rahmi, G., Gazeau, F., Wilhelm, C., Silva, A.K., Extracellular vesicles for personalized medicine: the input of physically triggered production, loading and theranostic properties. Adv. Drug Deliv. Rev. 138 (2019), 247–258.
Samaras, J.J., Abecasis, B., Serra, M., Ducci, A., Micheletti, M., Impact of hydrodynamics on ipsc-derived cardiomyocyte differentiation processes. J. Biotechnol. 287 (2018), 18–27.
Samaras, J.J., Ducci, A., Micheletti, M., Flow, suspension and mixing dynamics in dasgip bioreactors, Part 2. AIChE J., 66, 2020, e16999.
Samaras, J.J., Micheletti, M., Ducci, A., Suspension and mixing characterization of intermittent agitation modes in dasgip bioreactors. Chem. Eng. Technol. 42 (2019), 1587–1593.
Samaras, J.J., Micheletti, M., Ducci, A., Flow, suspension, and mixing dynamics in dasgip bioreactors: Part 1. AIChE J., 66, 2020, e17014.
Sion, C., Ghannoum, D., Ebel, B., Gallo, F., de Isla, N., Guedon, E., Chevalot, I., Olmos, E., A new perfusion mode of culture for wj-mscs expansion in a stirred and online monitored bioreactor. Biotechnol. Bioeng. 118 (2021), 4453–4464.
Sousa, M.F., Silva, M.M., Giroux, D., Hashimura, Y., Wesselschmidt, R., Lee, B., Roldão, A., Carrondo, M.J., Alves, P.M., Serra, M., Production of oncolytic adenovirus and human mesenchymal stem cells in a single-use, vertical-wheel bioreactor system: impact of bioreactor design on performance of microcarrier-based cell culture processes. Biotechnol. Prog. 31 (2015), 1600–1612.
Stolberg, S., McCloskey, K.E., Can shear stress direct stem cell fate?. Biotechnol. Prog. 25 (2009), 10–19.
Tan, K.Y., Reuveny, S., Oh, S.K.W., Recent advances in serum-free microcarrier expansion of mesenchymal stromal cells: parameters to be optimized. Biochem. Biophys. Res. Commun. 473 (2016), 769–773.
Wyrobnik, T.A., Ducci, A., Micheletti, M., Advances in human mesenchymal stromal cell-based therapies–towards an integrated biological and engineering approach. Stem Cell Res., 47, 2020, 101888.
Wysotzki, P., Sancho, A., Gimsa, J., Groll, J., A comparative analysis of detachment forces and energies in initial and mature cell-material interaction. Colloids Surf. B, Biointerfaces, 190, 2020, 110894.
Yuan, Y., Kallos, M.S., Hunter, C., Sen, A., Improved expansion of human bone marrow-derived mesenchymal stem cells in microcarrier-based suspension culture. J. Tissue Eng. Regen. Med. 8 (2014), 210–225.
