FEM-based oxygen consumption and cell viability models for avascular pancreatic islets.
BACKGROUND
The function and viability of cultured, transplanted, or encapsulated pancreatic islets is often limited by hypoxia because these islets have lost their vasculature during the isolation process and have to rely on gradient-driven passive diffusion, which cannot provide adequate oxygen transport. Pancreatic islets (islets of Langerhans) are particularly susceptible due to their relatively large size, large metabolic demand, and increased sensitivity to hypoxia. Here, finite element method (FEM) based multiphysics models are explored to describe oxygen transport and cell viability in avascular islets both in static and in moving culture media.


METHODS
Two- and three-dimensional models were built in COMSOL Multiphysics using the convection and diffusion as well as the incompressible Navier-Stokes fluid dynamics application modes. Oxygen consumption was assumed to follow Michaelis-Menten-type kinetics and to cease when local concentrations fell below a critical threshold; in a dynamic model, it was also allowed to increase with increasing glucose concentration.


RESULTS
Partial differential equation (PDE) based exploratory cellular-level oxygen consumption and cell viability models incorporating physiologically realistic assumptions have been implemented for fully scaled cell culture geometries with 100, 150, and 200 microm diameter islets as representative. Calculated oxygen concentrations and intra-islet regions likely to suffer from hypoxia-related necrosis obtained for traditional flask-type cultures, oxygen-permeable silicone-rubber membrane bottom cultures, and perifusion chambers with flowing media and varying incoming glucose levels are presented in detail illustrated with corresponding colour-coded figures and animations.


CONCLUSIONS
Results of the computational models are, as a first estimate, in good quantitative agreement with existing experimental evidence, and they confirm that during culture, hypoxia is often a problem for non-vascularised islet and can lead to considerable cell death (necrosis), especially in the core region of larger islets. Such models are of considerable interest to improve the function and viability of cultured, transplanted, or encapsulated islets. The present implementation allows convenient extension to true multiphysics applications that solve coupled physics phenomena such as diffusion and consumption with convection due to flowing or moving media.
Diabetes Research Institute and the Department of Molecular and Cellular Pharmacology, University of Miami, Miller School of Medicine, Miami, FL, USA. pbuchwald@med.miami.edu
Peter
P
Buchwald
D018929:Cell Culture Techniques; D002470:Cell Survival; D003198:Computer Simulation; D004058:Diffusion; D020342:Finite Element Analysis; D006801:Humans; D000860:Hypoxia; D007515:Islets of Langerhans / Q000166:cytology*; D007700:Kinetics; D008962:Models, Theoretical; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption; D012212:Rheology
D010100:Oxygen