FEM-based oxygen consumption and cell viability models for avascular pancreatic islets

Buchwald, Péter

doi:10.1186/1742-4682-6-5

Cited by 155 publications

(191 citation statements)

References 56 publications

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“…Another model by Johnson et al [140] predicts that even at surface density of 500 IEQ/cm 2 , the core of a standard encapsulated IEQ becomes hypoxic. These findings were confirmed in an independent mathematical model [145] . Islets cultured under normoxic conditions in 1 mm high standard culture medium at density of 1600 IEQ/cm 2 present hypoxic core when their size exceed a diameter of 100 μm.…”

Section: Barkai U Et Al Survival Of Encapsulated Isletssupporting

confidence: 73%

Survival of encapsulated islets: More than a membrane story

Barkai¹,

Rotem²,

Vos³

2016

WJT

114

109

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Section: Barkai U Et Al Survival Of Encapsulated Isletssupporting

confidence: 73%

Survival of encapsulated islets: More than a membrane story

Barkai¹,

Rotem²,

Vos³

2016

WJT

114

109

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“…The reduced growth rate of the immobilized cells could be explained by the presence of a dead cell core developed by the aggregates in both bead types (Fig. S2) that could be caused by nutrient limitations (Buchwald, 2009). The requirement for growing cells to counter opposing gel forces (Simpson et al, 2004;Stabler et al, 2001) could also have hindered immobilized cell expansion.…”

Section: Comparison Of the Emulsion Processes With The Extrusion Processmentioning

confidence: 98%

Pancreatic cell immobilization in alginate beads produced by emulsion and internal gelation

Hoesli¹,

Raghuram²,

Kiang³

et al. 2010

Biotech & Bioengineering

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Alginate has been used to protect transplanted pancreatic islets from immune rejection and as a matrix to increase the insulin content of islet progenitor cells. The throughput of alginate bead generation by the standard extrusion and external gelation method is limited by the rate of droplet formation from nozzles. Alginate bead generation by emulsion and internal gelation is a scaleable alternative that has been used with biological molecules and microbial cells, but not mammalian cells. We describe the novel adaptation of this process to mammalian cell immobilization. After optimization, the emulsion process yielded 90 ± 2% mouse insulinoma 6 (MIN6) cell survival, similar to the extrusion process. The MIN6 cells expanded at the same rate in both bead types to form pseudo-islets with increased glucose stimulation index compared to cells in suspension. The emulsion process was suitable for primary pancreatic exocrine cell immobilization, leading to 67 ± 32 fold increased insulin expression after 10 days of immobilized culture. Due to the scaleability and broad availability of stirred mixers, the emulsion process represents an attractive option for laboratories that are not equipped with extrusion-based cell encapsulators, as well as for the production of immobilized or encapsulated cellular therapeutics on a clinical scale.

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“…In particular, the volume of each system was divided in two sub-domains: (I) a fluid domain, in which no oxygen consumption occurs and where fluid dynamics as well as oxygen convective transport (i.e., diffusion + advection) were solved; and (II) a hydrogel construct domain which was treated as a solid region where only oxygen diffusion and consumption was solved, in agreement with [45,46]. Figure 5 shows the two sub-domains for the MCmB bioreactor.…”

Section: Computational Mass Transport and Flow Modelmentioning

confidence: 99%

Design Criteria for Generating Physiologically Relevant In Vitro Models in Bioreactors

2014

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Abstract:In this paper, we discuss the basic design requirements for the development of physiologically meaningful in vitro systems comprising cells, scaffolds and bioreactors, through a bottom up approach. Very simple micro-and milli-fluidic geometries are first used to illustrate the concepts, followed by a real device case-study. At each step, the fluidic and mass transport parameters in biological tissue design are considered, starting from basic questions such as the minimum number of cells and cell density required to represent a physiological system and the conditions necessary to ensure an adequate nutrient supply to tissues. At the next level, we consider the use of three-dimensional scaffolds, which are employed both for regenerative medicine applications and for the study of cells in environments which better recapitulate the physiological milieu. Here, the driving need is the rate of oxygen supply which must be maintained at an appropriate level to ensure cell viability throughout the thickness of a scaffold. Scaffold and bioreactor design are both critical in defining the oxygen profile in a cell construct and are considered together. We also discuss the oxygen-shear stress trade-off by considering the levels of mechanical stress required for hepatocytes, which are the limiting cell type in a multi-organ model. Similar considerations are also made for glucose consumption in cell constructs. Finally, the allometric approach for generating multi-tissue systemic models using bioreactors is described.

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FEM-based oxygen consumption and cell viability models for avascular pancreatic islets

Cited by 155 publications

References 56 publications

Survival of encapsulated islets: More than a membrane story

Survival of encapsulated islets: More than a membrane story

Pancreatic cell immobilization in alginate beads produced by emulsion and internal gelation

Design Criteria for Generating Physiologically Relevant In Vitro Models in Bioreactors

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