title: Efficient manufacturing of therapeutic mesenchymal stromal cells with the use of the Quantum Cell Expansion System.
abstract: BACKGROUND
  The use of bone marrow-derived mesenchymal stromal cells (MSCs) as a cellular therapy for various diseases, such as graft-versus-host disease, diabetes, ischemic cardiomyopathy and Crohn's disease, has produced promising results in early-phase clinical trials. However, for widespread application and use in later phase studies, manufacture of these cells must be cost-effective, safe and reproducible. Current methods of manufacturing in flasks or cell factories are labor-intensive, involve a large number of open procedures and require prolonged culture times.
  
  
  METHODS
  We evaluated the Quantum Cell Expansion System for the expansion of large numbers of MSCs from unprocessed bone marrow in a functionally closed system and compared the results with a flask-based method currently in clinical trials.
  
  
  RESULTS
  After only two passages, we were able to expand a mean of 6.6 × 10(8) MSCs from 25 mL of bone marrow reproducibly. The mean expansion time was 21 days, and cells obtained were able to differentiate into all three lineages: chondrocytes, osteoblasts and adipocytes. The Quantum was able to generate the target cell number of 2.0 × 10(8) cells in an average of 9 fewer days and in half the number of passages required during flask-based expansion. We estimated that the Quantum would involve 133 open procedures versus 54,400 in flasks when manufacturing for a clinical trial. Quantum-expanded MSCs infused into an ischemic stroke rat model were therapeutically active.
  
  
  CONCLUSIONS
  The Quantum is a novel method of generating high numbers of MSCs in less time and at lower passages when compared with flasks. In the Quantum, the risk of contamination is substantially reduced because of the substantial decrease in open procedures.
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, The Methodist Hospital, and Baylor College of Medicine, Houston, Texas, USA; Program for Cell Enhancement and Technologies for Immunotherapy, Sheikh Zayed Institute for Pediatric Surgical Innovation, and The Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC, USA. Electronic address: phanley@childrensnational.org.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Hanley
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, The Methodist Hospital, and Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Zhuyong
authors.initials: Z
authors.lastname: Mei
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, The Methodist Hospital, and Baylor College of Medicine, Houston, Texas, USA.
authors.forename: April G
authors.initials: AG
authors.lastname: Durett
authors.forename: Maria da Graca
authors.initials: Mda G
authors.lastname: Cabreira-Hansen
authors.affiliation: The Texas Heart Institute, St Luke's Episcopal Hospital, Houston, Texas, USA.
authors.forename: Marie da Graca
authors.initials: Mda G
authors.lastname: Cabreira-Harrison
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, The Methodist Hospital, and Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Mariola
authors.initials: M
authors.lastname: Klis
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, The Methodist Hospital, and Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, The Methodist Hospital, and Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Neurology, University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Neurology, University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Kaushik
authors.initials: K
authors.lastname: Parsha
authors.affiliation: Department of Neurology, University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Osman
authors.initials: O
authors.lastname: Mir
authors.affiliation: Department of Neurology, University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Farhaan
authors.initials: F
authors.lastname: Vahidy
authors.affiliation: University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA.
authors.forename: Debra
authors.initials: D
authors.lastname: Bloom
authors.affiliation: Terumo BCT, Lakewood, Colorado, USA.
authors.forename: R Brent
authors.initials: RB
authors.lastname: Rice
authors.affiliation: University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA.
authors.forename: Peiman
authors.initials: P
authors.lastname: Hematti
authors.affiliation: Department of Neurology, University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Sean I
authors.initials: SI
authors.lastname: Savitz
authors.affiliation: Center for Cell and Gene Therapy, Texas Children's Hospital, The Methodist Hospital, and Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Gee
mesh_terms: D000818:Animals; D019149:Bioreactors; D001854:Bone Marrow Cells / Q000166:cytology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage; D064987:Cell- and Tissue-Based Therapy; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051381:Rats
keywords: Quantum; cell culture expansion; good manufacturing practices; mesenchymal stromal cells; stroke
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