Bioreactor for Blood Product Production

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...

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Main Authors: Michael R. Doran B.Sc., B.Eng., Ph.D., Ian Alexander Aird, Flavia Marturana, Nicholas Timmins, Kerry Atkinson, Lars K. Nielsen
Format: Article
Language:English
Published: SAGE Publishing 2012-06-01
Series:Cell Transplantation
Online Access:https://doi.org/10.3727/096368911X627363
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author Michael R. Doran B.Sc., B.Eng., Ph.D.
Ian Alexander Aird
Flavia Marturana
Nicholas Timmins
Kerry Atkinson
Lars K. Nielsen
author_facet Michael R. Doran B.Sc., B.Eng., Ph.D.
Ian Alexander Aird
Flavia Marturana
Nicholas Timmins
Kerry Atkinson
Lars K. Nielsen
author_sort Michael R. Doran B.Sc., B.Eng., Ph.D.
collection DOAJ
description 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.
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spelling doaj.art-396211a8c8ee4b259e7b7d1ae46cf1252022-12-21T19:54:56ZengSAGE PublishingCell Transplantation0963-68971555-38922012-06-012110.3727/096368911X627363Bioreactor for Blood Product ProductionMichael R. Doran B.Sc., B.Eng., Ph.D.0Ian Alexander Aird1Flavia Marturana2Nicholas Timmins3Kerry Atkinson4Lars K. Nielsen5Stem Cell Therapies Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, AustraliaBioengineering Laboratory, Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, AustraliaBioengineering Laboratory, Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, AustraliaBioengineering Laboratory, Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, AustraliaAdult Stem Cell Laboratory, Mater Medical Research Institute, Brisbane, Queensland, AustraliaBioengineering Laboratory, Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, AustraliaThe 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.https://doi.org/10.3727/096368911X627363
spellingShingle Michael R. Doran B.Sc., B.Eng., Ph.D.
Ian Alexander Aird
Flavia Marturana
Nicholas Timmins
Kerry Atkinson
Lars K. Nielsen
Bioreactor for Blood Product Production
Cell Transplantation
title Bioreactor for Blood Product Production
title_full Bioreactor for Blood Product Production
title_fullStr Bioreactor for Blood Product Production
title_full_unstemmed Bioreactor for Blood Product Production
title_short Bioreactor for Blood Product Production
title_sort bioreactor for blood product production
url https://doi.org/10.3727/096368911X627363
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