Eliminating oxygen supply limitations for transplanted microencapsulated islets in the treatment of type 1 diabetes

Type I diabetes is a disease that results from a person's impaired ability to produce insulin, a protein that regulates the blood glucose concentration. Insulin is produced by [beta]-cells in the Islets of Langerhans, which are aggregates of cells averaging about 150 [mu]m in diameter and constituting about 1 to 2% of the pancreas volume. The efficacy of islet transplantation as a treatment for diabetes has been demonstrated in humans by the Edmonton Protocol, but obstacles remain for wide scale application. One major issue is that successful islet transplantation requires permanent use of multiple immunosuppressive agents. These agents may have serious side effects as well as a substantial financial burden. Microencapsulation is used for full or partial protection of transplanted islets from immune rejection. However, the microcapsule prevents islet revascularization and creates an additional mass transfer resistance for oxygen transport to islets. This reduced oxygen transfer can lead to a hypoxic core within the islet that results in tissue death and reduced function. We have studied two approaches to enhance microencapsulated islet survival and function by reducing oxygen transport limitations. The first method involves incorporating a perfluorocarbon emulsion into alginate microcapsules to enhance oxygen permeability in order to protect islets from hypoxia. The second method involves dispersing the islets into single cells and allowing them to reaggregate into cell clusters smaller than the original islet. The smaller aggregates are less prone to the development of a necrotic core and can function normally because of adequate oxygen supply and the presence of cell to cell contacts.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2008

Author dc:creator

• Lewis, Amy Suzanne

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/1721.1/42941

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/42941