VASCULARIZATION OF PURIFIED PANCREATIC ISLET-LIKE CELL AGGREGATES (PSEUDOISLETS) AFTER SYNGENEIC TRANSPLANTATION

To clarify whether avascular purified endocrine cell aggregates derive d from islets of Langerhans (pseudoislets) revascularize similarly to what is known for intact pancreatic islet grafts, we studied the proce ss of angiogenesis and revascularization of syngeneically transplanted pseudoislets using intravital fluorescence microscopy. Pseudoislets w ere composed of pure beta-cells (B) or non-beta-cells (NB), as well as of mixed beta- and non-beta-cells (B/NB; 70/30%) or non-sorted-cells (NC), and were transplanted into the dorsal skinfold of Syrian golden hamsters. Intact islet grafts served as controls. At day 6 after trans plantation, microvascularization of all types of pseudoislets was foun d to be less than in controls, as indicated by a reduced number of tra nsplants that contained newly formed microvessels (take-rate: B, 38.8; NE, 38.7; B/NB, 43.8; and NC, 40.3% vs. intact islet grafts, 71.9%; P < 0.01). Moreover, those pseudoislets that had developed a microvascu lar network revealed a significantly lower functional capillary densit y (145.8 +/- 49.5 to 241.0 +/- 47.5 cm(-1) vs. intact islet grafts: 45 9.8 +/- 65.6 cm(-1) P < 0.05). After 20 days, the take-rate of pseudoi slets was still lower (B, 67.4; NE, 45.3; B/NB, 48.4; and NC, 64.2%) w hen compared with intact islet grafts (88%; P < 0.05); however, islet- like aggregates with vascularization now showed an islet-specific glom erulus-like network of capillaries with a functional capillary density (498.5 +/- 49.1 to 601.4 +/- 124.0 cm(-1)) similar to that of intact islet grafts (644.3 +/- 26.8 cm(-1)). We conclude that the dissociatio n of pancreatic islets, followed by reaggregation of the purified endo crine cells to islet-like clusters (pseudoislets), delays the process of angiogenesis and revascularization after free transplantation; howe ver, this does not influence the capacity to form an intact islet-spec ific microvasculature (angio-architecture), which appears to be indepe ndent from the cellular composition of pseudoislets.