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Biochemical Engineering Journal
Vol. 108, 2016, Pages: 58–68

Evaluation of a monitored multiplate bioreactor for large-scale expansion of human periosteum derived stem cells for bone tissue engineering applications

T. Lambrechts, I. Papantoniou, S. Viazzi, T. Bovy, J. Schrooten, F.P. Luyten, J.-M. Aerts

Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Belgium.


In light of the large-scale expansion of human periosteum derived stem cells for the treatment of large bone defects, a multiplate bioreactor system (Pall Integrity Xpansion) in combination with an integrated holographic imaging platform (Ovizio iLine S microscope) was evaluated. The culture process was quantitatively characterized by imaging data, metabolite concentrations and a breakdown of the cell recovery fractions. The resulting cell quality was assessed based on the minimal criteria for mesenchymal stem cells, including viability on cell culture plastic, identity markers and tri-lineage differentiation potential. Additionally, an in vivo bone forming potency assay was used in an ectopic mice model that resulted in compelling bone formation (11.6 ± 3.1% and 12.8 ± 3.3% for the bioreactor and control tissue culture flask condition, respectively). Therefore, it was shown that the bioreactor is able to produce large quantities of cells, while maintaining satisfactory cell quality.

Graphical abstract

Keywords: Bioreactors; Scale-up; Bioprocess monitoring; Stem cell characterization; Tissue cell culture; In vivo bone formation.

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