title: Bioreactor for blood product production.
abstract: The feasibility of ex vivo blood production is limited by both biological and engineering challenges. From an engineering perspective, these challenges include the significant volumes required to generate even a single unit of a blood product, as well as the correspondingly high protein  consumption required for such large volume cultures. Membrane bioreactors, such as hollow fiber bioreactors (HFBRs), enable cell densities approximately 100-fold greater than traditional culture systems and therefore may enable a significant reduction in culture working volumes. As cultured  cells, and larger molecules, are retained within a fraction of the system volume, via a semipermeable membrane it may be possible to reduce protein consumption by limiting supplementation to only this fraction. Typically, HFBRs are complex perfusion systems having total volumes incompatible  with bench scale screening and optimization of stem cell-based cultures. In this article we describe the use of a simplified HFBR system to assess the feasibility of this technology to produce blood products from umbilical cord blood-derived CD34(+) hematopoietic stem progenitor cells  (HSPCs). Unlike conventional HFBR systems used for protein manufacture, where cells are cultured in the extracapillary space, we have cultured cells in the intracapillary space, which is likely more compatible with the large-scale production of blood cell suspension cultures. Using this platform  we direct HSPCs down the myeloid lineage, while targeting a 100-fold increase in cell density and the use of protein-free bulk medium. Our results demonstrate the potential of this system to deliver high cell densities, even in the absence of protein supplementation of the bulk medium.
authors.affiliation: Stem Cell Therapies Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia. michael.doran@qut.edu.au
authors.forename: Michael R
authors.initials: MR
authors.lastname: Doran
authors.forename: Ian Alexander
authors.initials: IA
authors.lastname: Aird
authors.forename: Flavia
authors.initials: F
authors.lastname: Marturana
authors.forename: Nicholas
authors.initials: N
authors.lastname: Timmins
authors.forename: Kerry
authors.initials: K
authors.lastname: Atkinson
authors.forename: Lars K
authors.initials: LK
authors.lastname: Nielsen
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D019149:Bioreactors; D039481:CD11b Antigen / Q000378:metabolism; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods*; D005312:Fetal Blood / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D016256:Lewis X Antigen / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D039481:CD11b Antigen; D016256:Lewis X Antigen