title: Packed Bed Bioreactor for the Isolation and Expansion of Placental-Derived Mesenchymal Stromal Cells.
abstract: Large numbers of Mesenchymal stem/stromal cells (MSCs) are required for clinical relevant doses to treat a number of diseases. To economically manufacture these MSCs, an automated bioreactor system will be required. Herein we describe the development of a scalable closed-system, packed bed bioreactor suitable for large-scale MSCs expansion. The packed bed was formed from fused polystyrene pellets that were air plasma treated to endow them with a surface chemistry similar to traditional tissue culture plastic. The packed bed was encased within a gas permeable shell to decouple the medium nutrient supply and gas exchange. This enabled a significant reduction in medium flow rates, thus reducing shear and even facilitating single pass medium exchange. The system was optimised in a small-scale bioreactor format (160 cm2) with murine-derived green fluorescent protein-expressing MSCs, and then scaled-up to a 2800 cm2 format. We demonstrated that placental derived MSCs could be isolated directly within the bioreactor and subsequently expanded. Our results demonstrate that the closed system large-scale packed bed bioreactor is an effective and scalable tool for large-scale isolation and expansion of MSCs.
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology at the Translational Research Institute, Brisbane, Queensland, Australia.|School of Chemistry, Physics and Mechanical Engineering, Science and Engineering Faculty, Queensland University of Technology Brisbane, Queensland, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Osiecki
authors.affiliation: Ian Wark Research Institute, University of South Australia. Adelaide, South Australia, Australia.|Mawson Institute, University of South Australia. Adelaide, South Australia, Australia.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Michl
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology at the Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Betul
authors.initials: B
authors.lastname: Kul Babur
authors.affiliation: Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran.
authors.forename: Mahboubeh
authors.initials: M
authors.lastname: Kabiri
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology at the Translational Research Institute, Brisbane, Queensland, Australia.|University of Queensland Centre for Clinical Research, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Kerry
authors.initials: K
authors.lastname: Atkinson
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology at the Translational Research Institute, Brisbane, Queensland, Australia.|School of Chemistry, Physics and Mechanical Engineering, Science and Engineering Faculty, Queensland University of Technology Brisbane, Queensland, Australia.
authors.forename: William B
authors.initials: WB
authors.lastname: Lott
authors.affiliation: Mawson Institute, University of South Australia. Adelaide, South Australia, Australia.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Griesser
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology at the Translational Research Institute, Brisbane, Queensland, Australia.|Mater Medical Research Institute, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Doran
mesh_terms: D050156:Adipogenesis; D000818:Animals; D019149:Bioreactors; D001854:Bone Marrow Cells / Q000166:cytology; D018929:Cell Culture Techniques / Q000295:instrumentation*; D002454:Cell Differentiation; D020219:Chondrogenesis; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D010012:Osteogenesis; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D010920:Placenta / Q000166:cytology*; D011137:Polystyrenes / Q000737:chemistry; D011247:Pregnancy
chemical_list: D011137:Polystyrenes; D049452:Green Fluorescent Proteins; D010100:Oxygen