title: Large-scale progenitor cell expansion for multiple donors in a monitored hollow fibre bioreactor.
abstract: 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).
  
  
  
  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.
  
  
  
  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 bone-forming 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.
authors.affiliation: Prometheus-Division of Skeletal Tissue Engineering, KU Leuven, Belgium; Division Animal and Human Health Engineering, KU Leuven, Belgium.
authors.forename: Toon
authors.initials: T
authors.lastname: Lambrechts
authors.affiliation: Prometheus-Division of Skeletal Tissue Engineering, KU Leuven, Belgium; Skeletal Biology and Engineering Research Centre, KU Leuven, Belgium.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Papantoniou
authors.affiliation: Terumo BCT, Inc., Lakewood, Colorado, USA.
authors.forename: Brent
authors.initials: B
authors.lastname: Rice
authors.affiliation: Prometheus-Division of Skeletal Tissue Engineering, KU Leuven, Belgium; Department of Materials Engineering, KU Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Schrooten
authors.affiliation: Prometheus-Division of Skeletal Tissue Engineering, KU Leuven, Belgium; Skeletal Biology and Engineering Research Centre, KU Leuven, Belgium.
authors.forename: Frank P
authors.initials: FP
authors.lastname: Luyten
authors.affiliation: Prometheus-Division of Skeletal Tissue Engineering, KU Leuven, Belgium; Division Animal and Human Health Engineering, KU Leuven, Belgium. Electronic address: jean-marie.aerts@biw.kuleuven.be.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Aerts
mesh_terms: D000328:Adult; D000818:Animals; D019149:Bioreactors; D001842:Bone and Bones / Q000166:cytology; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods; D002454:Cell Differentiation; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy; D005260:Female; D006801:Humans; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D010521:Periosteum / Q000166:cytology; D013234:Stem Cells / Q000166:cytology*; D055815:Young Adult
keywords: bioreactor; mesenchymal stromal cell expansion; osteogenesis; process monitoring and control; process reproducibility; quality control