[en] Mesenchymal stem cell (MSC) products are promising therapeutic candidates to treat a wide range of pathologies. The successful commercialization of these cell therapies will, however, depend on the development of reproducible cell production processes. For this, using microcarriers as growth supports within controlled conditions may be a viable process option. Although increasing microcarrier concentration may be associated with greater productivity due to the increased available culture surface, additional friction or shocks between microcarriers are likely to lead to undesired cell death. However, data detailing the impact of microcarrier collisions on MSC growth remains scarce. The following work demonstrates that MSC growth on microcarriers is greatly influenced by particle concentration even when little impact is observed on the apparent growth rate. It is suggested that the apparent growth rate may result in an equilibrium between growth and death kinetics which are independently affected by particle concentration and that certain MSC quality attributes may be progressively degraded in parallel. In addition, the theoretical reduction of the MSC growth rate was modeled according to the ratio between the average interparticle distance and the Kolmogorov scale. This study is an original contribution toward understanding the hydrodynamic effects in microcarrier-based stem cell cultures.
Disciplines :
Engineering, computing & technology: Multidisciplinary, general & others
Author, co-author :
Maillot, Charlotte ; Université de Liège - ULiège > Chemical engineering ; Laboratoire Reactions et Genie des Procedes, Universite de Lorraine, CNRS UMR 7274, Nancy, France
De Isla, Natalia; Department of Chemical Engineering, Product Environment and Processes (PEPs), Universite de Liege, Liege, Belgium
Loubiere, Celine; Laboratoire Reactions et Genie des Procedes, Universite de Lorraine, CNRS UMR 7274, Nancy, France
Toye, Dominique ; Université de Liège - ULiège > Department of Chemical Engineering > PEPs - Products, Environment, and Processes
Olmos, Eric ; Laboratoire Reactions et Genie des Procedes, Universite de Lorraine, CNRS UMR 7274, Nancy, France
Language :
English
Title :
Impact of microcarrier concentration on mesenchymal stem cell growth and death: Experiments and modeling.
The authors would like to thank Caroline Sion, Naceur Charif, Amandine May, and Mégane Jeannelle for their valuable technical support. This study was supported by Lorraine University of Excellence/PhD grant 2019/R01PJZHX.
Bianco, P., & Robey, P. G. (2001). Stem cells in tissue engineering. Nature, 414(6859), 118–121.
Chen, A. K.-L., Chew, Y. K., Tan, H. Y., Reuveny, S., & Weng Oh, S. K (2015). Increasing efficiency of human mesenchymal stromal cell culture by optimization of microcarrier concentration and design of medium feed. Cytotherapy, 17(2), 163–173.
Chen, A. K.-L., Reuveny, S., & Oh, S. K. W. (2013). Application of human mesenchymal and pluripotent stem cell microcarrier cultures in cellular therapy: Achievements and future direction. Biotechnology Advances, 31(7), 1032–1046.
Cherry, R. S., & Papoutsakis, E. T. (1986). Hydrodynamic effects on cells in agitated tissue culture reactors. Bioprocess Engineering, 1, 29–41.
Cherry, R. S., & Papoutsakis, E. T. (1988). Physical mechanisms of cell damage in microcarrier cell culture bioreactors. Biotechnology and Bioengineering, 32(8), 1001–1014.
Croughan, M. S. (1988). Hydrodynamic effects on animal cells in microcarrier bioreactors (Doctoral dissertation). Massachusetts Institute of Technology.
Croughan, M. S., Hamel, J.-F. P., & Wang, D. I. (1988). Effects of microcarrier concentration in animal cell culture. Biotechnology and Bioengineering, 32, 975–982.
Dominici, M., LeBlanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F., Krause, D., Deans, R., Keating, A., Prockop, D., & Horwitz, E. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. the International Society for Cellular Therapy position statement. Cytotherapy, 8, 315–317.
Engler, A. J., Sen, S., Sweeney, H. L., & Discher, D. E. (2006). Matrix elasticity directs stem cell lineage specification. Cell, 126, 677–689.
Frank, V., Kaufmann, S., Wright, R., Horn, P., Yoshikawa, H. Y., Wuchter, P., Madsen, J., Lewis, A. L., Armes, S. P., Ho, A. D., & Tanaka, M. (2016). Frequent mechanical stress suppresses proliferation of mesenchymal stem cells from human bone marrow without loss of multipotency. Scientific Reports, 6, 24264.
Godara, P., McFarland, C. D., & Nordon, R. E. (2008). Design of bioreactors for mesenchymal stem cell tissue engineering. Journal of Chemical Technology & Biotechnology, 83, 408–420.
Hewitt, C. J., Lee, K., Nienow, A. W., Thomas, R. J., Smith, M., & Thomas, C. R. (2011). Expansion of human mesenchymal stem cells on microcarriers. Biotechnology Letters, 33(11), 2325–2335.
Hoch, A. I., & Leach, J. K. (2014). Concise review: Optimizing expansion of bone marrow mesenchymal stem/stromal cells for clinical applications. Stem Cells Translational Medicine, 3, 643–652.
Hu, W. S., Meier, J., & Wang, D. I. C. (1985). A mechanistic analysis of the inoculum requirement for the cultivation of mammalian cells on microcarriers. Biotechnology and Bioengineering, 27, 585–595.
Huebsch, N., Arany, P. R., Mao, A. S., Shvartsman, D., Ali, O. A., Bencherif, S. A., Rivera-Feliciano, J., & Mooney, D. J. (2010). Harnessing traction-mediated manipulation of the cell/matrix interface to control stem-cell fate. Nature Materials, 9, 518–526.
Ikebe, C., & Suzuki, K. (2014). Mesenchymal stem cells for regenerative therapy: Optimization of cell preparation protocols. BioMed Research International, 2014, 951512.
Laner-Plamberger, S., Lener, T., Schmid, D., Streif, D. A., Salzer, T., Öller, M., Hauser-Kronberger, C., Fischer, T., Jacobs, V. R., Schallmoser, K., Gimona, M., & Rohde, E. (2015). Mechanical fibrinogen-depletion supports heparin-free mesenchymal stem cell propagation in human platelet lysate. Journal of Translational Medicine, 13, 354.
Loubière, C., Sion, C., De Isla, N., Reppel, L., Guedon, E., Chevalot, I., & Olmos, E. (2019). Impact of the type of microcarrier and agitation modes on the expansion performances of mesenchymal stem cells derived from umbilical cord. Biotechnology Progress, 35, e2887.
Maillot, C., Sion, C., De Isla, N., Toye, D., & Olmos, E. (2021). Quality by design to define critical process parameters for mesenchymal stem cell expansion. Biotechnology Advances, 50, 107765.
Martin, C. (2017). Étude des procédés daamplification de cellules souches mésenchymateuses humaines (Doctoral dissertation). Universite de Lorraine.
McKee, C., & Chaudhry, G. R. (2017). Advances and challenges in stem cell culture. Colloids and Surfaces B: Biointerfaces, 159, 62–77.
Mishra, R., Militky, J., Baheti, V., Huang, J., Kale, B., Venkataraman, M., Bele, V., Arumugam, V., Zhu, G., & Wang, Y. (2014). The production, characterization and applications of nanoparticles in the textile industry. Textile Progress, 46, 133–226.
Öncül, A. A. (2010). Simulation of interacting populations in inhomogeneous flows using reduced models (Doctoral dissertation). Otto von Guericke University Library.
Parekkadan, B., & Milwid, J. M. (2010). Mesenchymal stem cells as therapeutics. Annual Review of Biomedical Engineering, 12, 87–117.
Reppel, L. (2014). Potentialité des cellules stromales de la gelée de Wharton en ingénierie du cartillage (Doctoral dissertation). Universite de Lorraine.
Riazifar, M., Pone, E. J., Lötvall, J., & Zhao, W. (2017). Stem cell extracellular vesicles: Extended messages of regeneration. Annual Review of Pharmacology and Toxicology, 57, 125–154.
Ringe, J., Kaps, C., Burmester, G.-R., & Sittinger, M. (2002). Stem cells for regenerative medicine: Advances in the engineering of tissues and organs. Die Naturwissenschaften, 89(8), 338–351.
Rodriguez Fuentes, D. E., Fernández-Garza, L. E., Samia-Meza, J. A., Barrera-Barrera, S. A., Caplan, A. I., & Barrera-Saldaña, H. A. (2021). Mesenchymal stem cells current clinical applications: A systematic review. Archives of Medical Research, 52, 93–101.
Romani, P., Valcarcel-Jimenez, L., Frezza, C., & Dupont, S. (2021). Crosstalk between mechanotransduction and metabolism. Nature Reviews Molecular Cell Biology, 22, 22–38.
Russell, A. L., Lefavor, R. C., & Zubair, A. C. (2018). Characterization and cost-benefit analysis of automated bioreactor-expanded mesenchymal stem cells for clinical applications. Transfusion, 58, 2374–2382.
Sion, C., Loubière, C., Wlodarczyk-Biegun, M. K., Davoudi, N., Muller-Renno, C., Guedon, E., Chevalot, I., & Olmos, E. (2020). Effects of microcarriers addition and mixing on WJ-MSC culture in bioreactors. Biochemical Engineering Journal, 157, 107521.
Sion, C., Ghannoum, D., Ebel, B., Gallo, F., de Isla, N., Guedon, E., Chevalot, I., & Olmos, E. (2021). A new perfusion mode of culture for WJ-MSCs expansion in a stirred and online monitored bioreactor. Biotechnology and Bioengineering, 118(11), 4453–4464.
Trounson, A., & McDonald, C. (2015). Stem cell therapies in clinical trials: Progress and challenges. Cell Stem Cell, 17, 11–22.
Vining, K. H., & Mooney, D. J. (2017). Mechanical forces direct stem cell behaviour in development and regeneration. Nature Reviews Molecular Cell Biology, 18, 728–742.
Zhu, A. J., Haase, I., & Watt, F. M. (1999). Signaling via β1 integrins and mitogen-activated protein kinase determines human epidermal stem cell fate in vitro. Proceedings of the National Academy of Sciences of the United States of America, 96, 6728–6733.
Zwietering, T. (1958). Suspending of solid particles in liquid by agitators. Chemical Engineering Science, 8, 244–253.