Large-scale progenitor cell expansion for multiple donors in a monitored hollow fibre bioreactor

Background aims. With the increasing scale in stem cell production, a robust and controlled cell expansion process becomes essential for the clinical application of cell-based therapies.The objective of this work was the assessment of a hollow fiber bioreactor (Quantum Cell Expansion System from Terumo BCT) as a cell production unit for the clinical-scale production of human periosteum derived stem cells (hPDCs). Methods. We aimed to demonstrate comparability of bioreactor production to standard culture flask production based on a product characterization in line with the International Society of Cell Therapy in vitro benchmarks and supplemented with a compelling quantitative in vivo bone-forming potency assay. Multiple process read-outs were implemented to track process performance and deal with donor-to-donor-related variation in nutrient needs and harvest timing. Results. The data show that the hollow fiber bioreactor is capable of robustly expanding autologous hPDCs on a clinical scale (yield between 316 million and 444 million cells starting from 20 million after ± 8 days of culture) while maintaining their in vitro quality attributes compared with the standard flask-based culture. The in vivo boneforming assay on average resulted in 10.3 ± 3.7% and 11.0 ± 3.8% newly formed bone for the bioreactor and standard culture flask respectively.The analysis showed that the Quantum system provides a reproducible cell expansion process in terms of yields and culture conditions for multiple donors.publisher: Elsevier articletitle: Large-scale progenitor cell expansion for multiple donors in a monitored hollow fibre bioreactor journaltitle: Cytotherapy articlelink: http://dx.doi.org/10.1016/j.jcyt.2016.05.013 content_type: article copyright: © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.status: publishe