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- Title
Reducing Oxygen Limitations to Microencapsulated Islet Tissue by Dispersion and Reaggregation.
- Authors
O'Sullivan, Esther S.; Lewis, Amy S.; Omer, Abdulkadir; Lock, Jennifer; Bonner-Weir, Susan; Colton, Clark K.; Weir, Gordon C.
- Abstract
While microencapsulation protects transplanted tissue from the immune system, it also creates an additional mass transfer resistance for oxygen transport to the islets, with resultant hypoxia and necrosis. We predict based on theoretical modeling and calculated oxygen partial pressure profiles that in low oxygen environments islet tissue distributed as small clumps of cells or aggregates (37.5µm, 50µm or 75µm diameter) in a microcapsule (500µm diameter) would survive and function better than an intact whole islet (an islet equivalent, IE, of 150µm diameter); this advantage should occur even when the aggregate packing density is increased to 6 to 8 IE per capsule, with greatest packing density possible for the smallest aggregates. To test these predictions, alginate microcapsules containing Lewis rat islet tissue either as whole islets or small aggregates were transplanted intraperitoneally to ICR-scid mice and recovered 8 weeks later. Aggregates (average diameter 40µm) were formed by reaggregation of dispersed islet cells. Total tissue content per capsule (n=l 5) was determined by DNA assay before and after transplantation. Aggregate tissue content tended to be lower than islet tissue content (8.7±0.8 (SEM) vs 11.6±1.5 ng DNA respectively pre-transplant p=0.09; 6.4±0.5 vs 8.0±0.8 post-transplant, p=0.15). However, insulin content in the same capsules was comparable (32.7±2.5 vs 29.1±1.4 ng pre-transplant, p=0.39; 38.1±2.6 vs 31.2±3.6, post-transplant, p=0.23). Insulin to DNA ratio per capsule was significantly greater for the aggregate tissue post-transplant, but not pre-transplant (4.2±0.4 vs 3.3±0.4 pre-transplant, p=0.17; 6.2±0.3 vs 4.2±0.4 post-transplant, p=0.002), 1µm sections of encapsulated tissue recovered 2 weeks after similar transplants in syngeneic rats showed a greater incidence of central necrosis in the whole islets than in the aggregates. We conclude that the use of islet aggregates successfully reduces oxygen limitations during encapsulation, resulting in enhanced islet tissue survival and function on transplantation. This strategy has the potential to improve both the potency and packing density of encapsulated islet tissue.
- Subjects
PHYSIOLOGICAL transport of oxygen; MICROENCAPSULATION; TISSUES; ISLANDS of Langerhans transplantation; TRANSPLANTATION immunology; LABORATORY rats
- Publication
Diabetes, 2007, Vol 56, pA524
- ISSN
0012-1797
- Publication type
Article