An investigation of the diffusion‐limited growth of animal cells around single hollow fibers

Sardonini, Charles A.; DiBiasio, David

doi:10.1002/bit.260401013

Cited by 36 publications

(20 citation statements)

References 28 publications

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“…17,18 Agarose or gelatin/agarose cell immobilization has been used to investigate mass transfer or cell concentration gradients in HFBRs. [19][20][21] However, these systems were not designed for cell recovery.…”

Section: Introductionmentioning

confidence: 99%

A novel alginate hollow fiber bioreactor process for cellular therapy applications

Hoesli

Luu

Piret

2009

Biotechnology Progress

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Gel-matrix culture environments provide tissue engineering scaffolds and cues that guide cell differentiation. For many cellular therapy applications such as for the production of islet-like clusters to treat Type 1 diabetes, the need for large-scale production can be anticipated. The throughput of the commonly used nozzle-based devices for cell encapsulation is limited by the rate of droplet formation to approximately 0.5 L/h. This work describes a novel process for larger-scale batch immobilization of mammalian cells in alginate-filled hollow fiber bioreactors (AHFBRs). A methodology was developed whereby (1) alginate obstruction of the intra-capillary space medium flow was negligible, (2) extra-capillary alginate gelling was complete and (3) 83 +/- 4% of the cells seeded and immobilized were recovered from the bioreactor. Chinese hamster ovary (CHO) cells were used as a model aggregate-forming cell line that grew from mostly single cells to pancreatic islet-sized spheroids in 8 days of AHFBR culture. CHO cell growth and metabolic rates in the AHFBR were comparable to small-scale alginate slab controls. Then, the process was applied successfully to the culture of primary neonatal pancreatic porcine cells, without significant differences in cell viability compared with slab controls. As expected, alginate-immobilized culture in the AHFBR increased the insulin content of these cells compared with suspension culture. The AHFBR process could be refined by adding matrix components or adapted to other reversible gels and cell types, providing a practical means for gel-matrix assisted cultures for cellular therapy.

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Section: Introductionmentioning

confidence: 99%

A novel alginate hollow fiber bioreactor process for cellular therapy applications

Hoesli

Luu

Piret

2009

Biotechnology Progress

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“…Therefore, in this paper, the performance of hybridoma cells in a HFBR system was analyzed as a case study of cell culture in a membrane reactor. Modelling is increasingly being used to understand bioreactor behaviour, specifically some attempts to model hybridoma growth 23,24 and MAb production 25,26 in HFBR have been carried out. Moreover, different authors have recently proposed sophisticated mathematical equations to describe hybridoma metabolism and antibody production in batch cultures 19,20 .…”

Section: Jain and Kumarmentioning

confidence: 99%

Diffusion and Inhibition Processes in a Hollow-fiber Membrane Bioreactor for Hybridoma Culture. Development of a Mathematical Model

Legazpi

Laca

Collado

et al. 2016

Chem.Biochem.Eng.Q.

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The performance of a hollow-fiber membrane bioreactor (HFBR) (molecular weight cut-off 30 kD, fiber surface area 2050 cm 2 ) containing a culture of hybridoma cells has been investigated. Experimental data were used as basis to develop a model of general application. Concentrations of fundamental nutrients (glucose and glutamine), inhibitory products (ammonium and lactate), and monoclonal antibodies (MAb) against bovine lactoferrin (IgG 1 ) were monitored over time. Exchange of nutrients and products occurred across the capillary surface, whereas cells and MAb remained in the extra-capillary space (ECS). A protein-free culture medium (Hybrimax) with and without antibiotics was used. In both cases, the final MAb concentration was the same; however, antibiotic presence slowed down the time to achieve this concentration. Diffusion assays have been carried out in order to support the development of a mathematical model that describes the performance of the HFBR, including mass transfer and reaction terms. Inhibition by ammonium and lactate has been considered in the kinetics, providing model results consistent with experimental data. Further research with other cell lines and/or culture media will allow to broaden the field of application of this model for general use in HFBR systems.

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“…These gradients may be macroscopic (e.g., steady-state axial and radial gradients of nutrients and waste products in an HFBR [Chresand et al, 1988]), or microscopic (e.g., within the matrix in which the cells are growing). For example, oxygen gradients around single ®bers within an HFBR have been shown to limit the thickness of the cell layer growing around the ®ber (Sardonini and DiBiasio, 1992). In the case of chondrocyte growth in polymer scaolds, which are being used as bioarti®cial tissue constructs, there is evidence that diusion of nutrients within the extracellular matrix is a major factor limiting cell growth and matrix deposition (Freed et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Measurement of bioreactor perfusion using dynamic contrast agent‐enhanced magnetic resonance imaging

Thelwall

Neves²,

Brindle³

2001

Biotech & Bioengineering

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Dynamic magnetic resonance imaging was used to monitor solute diffusion through aggregates of Chinese hamster ovary cells growing on macroporous carriers in a fixed-bed bioreactor. Diffusion-weighted (1)H magnetic resonance imaging (MRI) and scanning electron microscopy demonstrated that cell growth in the bioreactor was heterogeneous, with the highest cell densities being found at the periphery of the carriers. T(1)-weighted magnetic resonance imaging measurements of the inflow of a commonly used magnetic resonance contrast agent, gadolinium-diethylenetriaminopentaacetic acid (Gd-DTPA), showed that migration of the agent through the peripheral cell masses could be explained by diffusion. However, appearance of the contrast agent in the center of the carriers was too fast to be explained by simple diffusion and indicated that these regions were perfused by convective flow. The average diffusivity of Gd-DTPA through the cell mass was found to be (2.4 +/- 0.2) x 10(-10) m(2) sec(-) (mean +/- SEM). This technique will be useful in the characterization and development of high-cell-density bioreactor systems, in which solute transport plays a critical role in cell growth and physiology.

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An investigation of the diffusion‐limited growth of animal cells around single hollow fibers

Cited by 36 publications

References 28 publications

A novel alginate hollow fiber bioreactor process for cellular therapy applications

A novel alginate hollow fiber bioreactor process for cellular therapy applications

Diffusion and Inhibition Processes in a Hollow-fiber Membrane Bioreactor for Hybridoma Culture. Development of a Mathematical Model

Measurement of bioreactor perfusion using dynamic contrast agent‐enhanced magnetic resonance imaging

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