title: Genetic stability of bone marrow-derived human mesenchymal stromal cells in the Quantum System.
abstract: OBJECTIVE
  The Quantum® Cell Expansion System (Quantum; Terumo BCT, Inc, Lakewood, CO, USA) is a novel hollow fiber-based device that automates and closes the cell culture process, reducing labor intensive tasks such as manual cell culture feeding and harvesting. The manual cell selection and expansion processes for the production of clinical-scale quantities of bone marrow-derived human mesenchymal stromal cells (BM-hMSCs) have been successfully translated onto the Quantum platform previously. The formerly static, manual, in vitro process performed primarily on tissue culture polystyrene substrates may raise the question of whether BM-hMSCs cultured on a hollow fiber platform yields comparable cell quality.
  
  
  METHODS
  A rigorous battery of assays was used to determine the genetic stability of BM-hMSCs selected and produced with the Quantum. In this study, genetic stability was determined by assessing spectral karyotype, micronucleus formation and tumorigenicity to resolve chromosomal aberrations in the stem cell population. Cell phenotype, adherent growth kinetics and tri-lineage differentiation were also evaluated. HMSC bone marrow aspirates, obtained from three approved donors, were expanded in parallel using T225 culture flasks and the Quantum.
  
  
  RESULTS
  BM-hMSCs harvested from the Quantum demonstrated immunophenotype, morphology and tri-lineage differentiation capacity characteristics consistent with the International Society of Cell Therapy standard for hMSCs. Cell populations showed no malignant neoplastic formation in athymic mice 60 days post-transplant, no clonal chromosomal aberrations were observed and no DNA damage was found as measured by micronucleus formation.
  
  
  CONCLUSIONS
  Quantum-produced BM-hMSCs are of comparable quality and demonstrate analogous genetic stability to BM-hMSCs cultured on tissue culture polystyrene substrates.
authors.affiliation: Terumo BCT, Inc, Lakewood, Colorado, USA. Electronic address: mark.jones@terumobct.com.
authors.forename: Mark
authors.initials: M
authors.lastname: Jones
authors.forename: Marileila
authors.initials: M
authors.lastname: Varella-Garcia
authors.forename: Margaret
authors.initials: M
authors.lastname: Skokan
authors.forename: Steven
authors.initials: S
authors.lastname: Bryce
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schowinsky
authors.forename: Rebecca
authors.initials: R
authors.lastname: Peters
authors.forename: Boah
authors.initials: B
authors.lastname: Vang
authors.forename: Michelle
authors.initials: M
authors.lastname: Brecheisen
authors.forename: Thomas
authors.initials: T
authors.lastname: Startz
authors.forename: Nathan
authors.initials: N
authors.lastname: Frank
authors.forename: Brian
authors.initials: B
authors.lastname: Nankervis
mesh_terms: D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D063646:Carcinogenesis; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020219:Chondrogenesis; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D042822:Genomic Instability / Q000235:genetics*; D064593:Heterografts; D006801:Humans; D059785:Karyotype; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D046509:Tissue Culture Techniques / Q000379:methods*; D055815:Young Adult
keywords: cell proliferation; chromosome; mesenchymal stromal cell; micronucleus; spectral karyotyping; xenograft