C. Beger et al., VASCULARIZATION OF PURIFIED PANCREATIC ISLET-LIKE CELL AGGREGATES (PSEUDOISLETS) AFTER SYNGENEIC TRANSPLANTATION, Diabetes, 47(4), 1998, pp. 559-565
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.