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A Spatiotemporal Microenvironment Model to Improve Design of a Three-Dimensional Bioreactor for Red Cell Production

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  • معلومة اضافية
    • بيانات النشر:
      Mary Ann Liebert Inc
    • الموضوع:
      2022
    • Collection:
      Queensland University of Technology: QUT ePrints
    • نبذة مختصرة :
      Cellular microenvironments provide stimuli including paracrine and autocrine growth factors and physico-chemical cues, which support efficient in vivo cell production unmatched by current in vitro biomanufacturing platforms. While three-dimensional (3D) culture systems aim to recapitulate niche architecture and function of the target tissue/organ, they are limited in accessing spatiotemporal information to evaluate and optimize in situ cell/tissue process development. Herein, a mathematical modelling framework is parameterized by single-cell phenotypic imaging and multiplexed biochemical assays to simulate the non-uniform tissue distribution of nutrients/metabolites and growth factors in cell niche environments. This model is applied to a bone marrow mimicry 3D perfusion bioreactor containing dense stromal and hematopoietic tissue with limited red blood cell (RBC) egress. The model characterized an imbalance between endogenous cytokine production and nutrient starvation within the microenvironmental niches and recommended increased cell inoculum density and enhanced medium exchange, guiding the development of a miniaturized prototype bioreactor. The second-generation prototype improved the distribution of nutrients and growth factors and supported a 50-fold increase in RBC production efficiency. This image-informed bioprocess modelling framework leverages spatiotemporal niche information to enhance biochemical factor utilization and improve cell manufacturing in 3D systems.
    • File Description:
      application/pdf
    • Relation:
      https://eprints.qut.edu.au/210657/1/AllenbyEPrint.pdf; Allenby, Mark, Okutsu, Naoki, Brailey, Kate, Guasch, Joana, Zhang, Qiming, Panoskaltsis, Nicki, & Mantalaris, Athanasios (2022) A Spatiotemporal Microenvironment Model to Improve Design of a Three-Dimensional Bioreactor for Red Cell Production. Tissue Engineering, Part A, 28(1-2), pp. 38-53.; https://eprints.qut.edu.au/210657/; Centre for Biomedical Technologies; Faculty of Engineering; School of Mechanical, Medical & Process Engineering
    • Rights:
      free_to_read ; http://creativecommons.org/licenses/by-nc/4.0/ ; Mary Ann Liebert, Inc. ; This work is covered by copyright. Unless the document is being made available under a Creative Commons Licence, you must assume that re-use is limited to personal use and that permission from the copyright owner must be obtained for all other uses. If the document is available under a Creative Commons License (or other specified license) then refer to the Licence for details of permitted re-use. It is a condition of access that users recognise and abide by the legal requirements associated with these rights. If you believe that this work infringes copyright please provide details by email to qut.copyright@qut.edu.au
    • الرقم المعرف:
      edsbas.82A4572E