Angiogenesis and Hemodynamics of Microvasculature of Transplanted Islets of Langerhans

Abstract

Transplantation of isolated islets of Langerhans is frequently followed by early loss of islet function. Because whether this is caused by insufficient vascularization or graft rejection is unknown, angiogenesis and microvascularization of islet grafts were studied in vivo by means of intravital microscopy. After transplantation of syngeneic islets in hamster dorsal skin-fold chambers, 97% (n = 66) of the islets exhibited the first signs of angiogenesis at days 2-4, characterized by sinusoidal sacculations and capillary sprouts. After 10 days, angiogenesis was completed, consisting of a microvascular network similar to those of islets in situ: arterial supply, afferent and efferent capillary loops, and venular drainage. Functional density of microvessels was 700.1 +/- 127.0 cm-1, and erythrocyte velocity was 0.58 +/- 0.35 mm/s. Intracellular insulin was demonstrated immunohistochemically. Electron-microscopic studies revealed normal fine structure of the capillary wall. The model allows in vivo analysis of microvascular phenomena occurring in host-vs.-graft reaction after allogeneic and xenogeneic islet transplantation. Furthermore, it may be used to quantitatively assess immunosuppressive regimens.

Vascular endothelial growth factor as a survival factor for human islets: effect of immunosuppressive drugs

“…Although the evidence for an autocrine survival pathway in no way reduces the likely importance of the VEGF-induced revascularisation of transplanted islets, capillary sprouting does not start until day 3 or 4 post-isolation [37], by which time more than one-half of the infused islets have been destroyed. VEGF 165 may therefore have a double protective action by increasing islet survival early after transplantation and then promoting the revascularisation of those surviving islets.…”

Improved outcome of islet transplantation in insulin-treated diabetic mice: effects on beta-cell mass and function

“…In insulin-treated mice, transplanted islets had to maintain, but not restore, normoglycaemia. On the other hand, when insulin implants were removed 14 days after transplantation, transplanted islets were already vascularized [28] and able to sense and respond more appropriately to changes in blood glucose than freshly transplanted,…”

Better vascular engraftment and function in pancreatic islets transplanted without prior culture

“…The islet capillary system is, however, disrupted by isolation, and during in vitro culture islet endothelial cells de-differentiate or die [9][10][11]. The revascularisation process of islets is generally thought to occur over a period of 7-14 days post-transplantation [12][13][14]. The newly formed blood vessels were earlier considered to originate from recipient blood ves-sels [15].…”