ABSTRACT
I. Introduction ..................................................................................................................... 585
II. Exogenous Insulin Delivery ........................................................................................... 586
III. Tissue Sources ................................................................................................................ 587
A. Xenogeneic Islets .................................................................................................... 587
B. Stem Cells ............................................................................................................... 588
C. Cell Lines ................................................................................................................ 588
IV. Immune Destruction of Islets ......................................................................................... 589
A. Auto-Immune Reactions ......................................................................................... 589
B. Allograft Reactions ................................................................................................. 590
C. Xenograft Reactions ............................................................................................... 590
D. Inflammatory Reactions .......................................................................................... 590
V. Engineering Approaches to Immunoprotection of Islets ............................................... 591
A. Extravascular Macroencapsulation Devices ........................................................... 591
B. Microencapsulation ................................................................................................. 593
1. Alginate and Poly-L-lysine .............................................................................. 593
2. Alginate Alone ................................................................................................. 594
3. Other Alginate Systems ................................................................................... 595
4. Other Microencapsulation Materials ............................................................... 595
5. In Vivo Performance of Microencapsulated Islets .......................................... 596
C. Mass Transfer ......................................................................................................... 596
1. Mass Transfer Limitations ............................................................................... 596
2. Methods to Improve Mass Transfer ................................................................ 598
D. NMR Spectroscopy and Imaging ........................................................................... 599
VI. Future Directions ............................................................................................................ 599
References ................................................................................................................................... 600
Type 1 diabetes is a disease that results from a person’s impaired ability to produce insulin, a
protein that regulates blood glucose concentration. Insulin is produced by b-cells in the Islets of
Langerhans, which are aggregates of cells averaging about 150 mm in diameter and constituting
about 1 to 2% of the pancreas volume. Type 1 diabetes is caused by auto-immune attack and
destruction of the b-cells, which compose about 80% of the islets. Diabetes has a serious impact on
the health care system. In 2002, there were an estimated 12.1 million people diagnosed (and about
50% more undiagnosed) with diabetes in the U.S. This number is expected to grow to 17.4 million
by 2020.
