Oxygen diffusion limitations in pancreatic islet culture and immunoisolation

Data for oxygen consumption by rat islets of Langerhans in a batch microreactor were fitted using a numerical solution of the transient oxygen diffusion-reaction equation. Average best-fit values were 3.1 +/- 0.7 x 10-8 mol/cm3-s for the maximum oxygen consumption rate Vmax in aminoacid-free media and 1.2 +/- 0.4 x 10-14 mol/cm-mm Hg-s for the oxygen permeability in islet tissue. These parameter values, along with a 30-60% positive correction for the presence of aminoacids in Vmax, were used to predict oxygen profiles inside and around islets under perifusion, culture, and immunoisolation conditions. The difference between Michaelis-Menten and zero-order kinetics and the role of the necrosis process in modeling of oxygen profiles were found to increase with the severity of hypoxia. Internal and external diffusion limitations were characterized for homogeneously dispersed tissue. Oxygen profiles were determined with finite differences in perifused rat islets for which second-phase insulin secretion data were available. Data were fitted with ad hoc kinetic models describing the effect of local pO2 on insulin secretion. A two-step, one-parameter model that assumed that local insulin secretion rate as a function of local pO2 is first-order for pO2 < P and zero-order for PO2 > P* resulted in the best data fit for P* values between 2 and 10 mm Hg, depending on the value of Vmax used. Oxygen profiles were estimated with finite elements for the axi-symmetric problem of single islet culture and the model did an excellent job in predicting loss of viability data, obtained using Trypan blue staining,

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2002

Author dc:creator

• Avgoustiniatos, Efstathios S

Advisor dc:contributor.advisor

• Clark K. Colton.

• Chemical Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/8269

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/8269