Experimental and theoretical considerations on oxygen supply for animal cell growth in fixed-bed reactors

Fassnacht, D.; Pörtner, Ralf

doi:10.1016/s0168-1656(99)00129-7

Cited by 81 publications

(52 citation statements)

References 35 publications

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“…In addition to scaffold-based approaches, 3D MSC expansion can also occur in suspension [38,83] and within spheroids [40]. 3D MSC expansion has been paired with dynamic stimulation because cell viability is restricted to 100-200 mm from the surface because of diffusive nutrient transport limitations when cultured statically [84]. Bioreactors are devices that facilitate the development of biological and/or biochemical processes through closely monitored and user-controlled operating parameters such as pH, temperature, nutrient supply, and waste removal [85].…”

Section: D Expansionmentioning

confidence: 99%

Concise Review: Optimizing Expansion of Bone Marrow Mesenchymal Stem/Stromal Cells for Clinical Applications

Hoch¹,

Leach²

2015

Stem Cells Translational Medicine

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Bone marrow-derived mesenchymal stem/stromal cells (MSCs) have demonstrated success in the clinical treatment of hematopoietic pathologies and cardiovascular disease and are the focus of treating other diseases of the musculoskeletal, digestive, integumentary, and nervous systems. However, during the requisite two-dimensional (2D) expansion to achieve a clinically relevant number of cells, MSCs exhibit profound degeneration in progenitor potency. Proliferation, multilineage potential, and colony-forming efficiency are fundamental progenitor properties that are abrogated by extensive monolayer culture. To harness the robust therapeutic potential of MSCs, a consistent, rapid, and minimally detrimental expansion method is necessary. Alternative expansion efforts have exhibited promise in the ability to preserve MSC progenitor potency better than the 2D paradigm by mimicking features of the native bone marrow niche. MSCs have been successfully expanded when stimulated by growth factors, under reduced oxygen tension, and in three-dimensional bioreactors. MSC therapeutic value can be optimized for clinical applications by combining system inputs to tailor culture parameters for recapitulating the niche with probes that nondestructively monitor progenitor potency. The purpose of this review is to explore how modulations in the 2D paradigm affect MSC progenitor properties and to highlight recent efforts in alternative expansion techniques. STEM CELLS TRANSLATIONAL MEDICINE 2014;3:643-652

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Section: D Expansionmentioning

confidence: 99%

Concise Review: Optimizing Expansion of Bone Marrow Mesenchymal Stem/Stromal Cells for Clinical Applications

Hoch¹,

Leach²

2015

Stem Cells Translational Medicine

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“…Direct axial perfusion of 3D porous constructs with medium in axial-flow packed bed bioreactors (aPBBs) uses convection to enhance oxygen and nutrients transport to cells internal to the construct [24][25][26][27]. However, at low axial superficial velocity the dissolved oxygen and nutrients concentrations may steeply decrease towards the end of the construct leading to poor cell nourishment and causing the formation of a necrotic end zone [28,29]. Cell perfusion at high axial superficial velocity to keep cells viable and differentiated anywhere in the construct may cause cell wash-out [30].…”

Section: Introductionmentioning

confidence: 99%

Model-Based Optimization of Scaffold Geometry and Operating Conditions of Radial Flow Packed-Bed Bioreactors for Therapeutic Applications

2014

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Abstract:Radial flow perfusion of cell-seeded hollow cylindrical porous scaffolds may overcome the transport limitations of pure diffusion and direct axial perfusion in the realization of bioengineered substitutes of failing or missing tissues. Little has been reported on the optimization criteria of such bioreactors. A steady-state model was developed, combining convective and dispersive transport of dissolved oxygen with Michaelis-Menten cellular consumption kinetics. Dimensional analysis was used to combine more effectively geometric and operational variables in the dimensionless groups determining bioreactor performance. The effectiveness of cell oxygenation was expressed in terms of non-hypoxic fractional construct volume. The model permits the optimization of the geometry of hollow cylindrical constructs, and direction and magnitude of perfusion flow, to ensure cell oxygenation and culture at controlled oxygen concentration profiles. This may help engineer tissues suitable for therapeutic and drug screening purposes. Greek Symbols Keywords

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“…Nevertheless, the fixed-bed bioreactor presents some drawbacks, such as a difficult monitoring of the cell concentration in the fixed-bed during the process and the presence of cell concentration gradients (Fassnacht et al 1999;Warnock et al 2005). The homogeneity of the cell concentration in the fixed-bed during the whole process is very important to reach the best yield of the bioreactor (Sadettin et al 2005;Nienow 2006).…”

Section: Introductionmentioning

confidence: 99%

“…A mathematical model of this fixed-bed bioreactor can be used to improve the control of the bioreactor and can contribute to the efficiency definition of the operating conditions leading to the homogeneity of the cell concentration in the fixed-bed. The gradients of the cell and the extracellular species concentrations inside a single carrier have been considered in several models developed in previous works (Tramper 1995;Fassnacht et al 1999;Pörtner et al 2005). The extrapolation from a single carrier to a stacking of carriers is seldom reported in the literature.…”

Section: Introductionmentioning

confidence: 99%

Segregated Model of Adherent Cell Culture in a Fixed-Bed Bioreactor

Gelbgras¹,

Wylock²,

Drugmand³

et al. 2011

Chemical Product and Process Modeling

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In this work, a mathematical model of a fixed-bed bioreactor for the animal cell culture is developed to study the optimization and the scale-up of this bioreactor. Several cell populations are considered: the cells in suspension in the medium at the beginning of the process and the adhering cells to the fixed-bed. The model includes a capture rate kinetic of the cells in suspension by the fixed-bed and a spatial distribution of the nutrient and by-product concentrations in the fixed-bed. Therefore, the model reports the potential gradients of the cell concentrations in the fixed-bed. Some model parameters are experimentally identified and the model is validated using experimental data obtained with two pilot bioreactors. The model is used as a simulation tool to study the influence of the bioreactor design or the velocity field of the culture medium on the cell concentration gradients in the fixed-bed bioreactor and to optimize the operating conditions, the design, and the scale-up of this bioreactor.

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Experimental and theoretical considerations on oxygen supply for animal cell growth in fixed-bed reactors

Cited by 81 publications

References 35 publications

Concise Review: Optimizing Expansion of Bone Marrow Mesenchymal Stem/Stromal Cells for Clinical Applications

Concise Review: Optimizing Expansion of Bone Marrow Mesenchymal Stem/Stromal Cells for Clinical Applications

Model-Based Optimization of Scaffold Geometry and Operating Conditions of Radial Flow Packed-Bed Bioreactors for Therapeutic Applications

Segregated Model of Adherent Cell Culture in a Fixed-Bed Bioreactor

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