Angiogenesis and angioarchitecture of transplanted fetal porcine islet-like cell clusters.

Abstract

Normoglycemic, athymic nude mice were implanted with 3 microl (approximately 250) fetal, porcine islet-like cell clusters under the renal capsule. The angioarchitecture of the transplanted islets was studied by microvascular corrosion casts 3 or 52 weeks after implantation. Arterioles were few, and observed mainly in the older age group. This is likely to be due to the fact that the arterioles were derived from intrarenal blood vessels, i.e., they were not visible on the graft surface. Within the grafts nests of capillaries, probably supplying a single islet-like cell clusters, could be seen in both groups. Numerous capillary sprouts were seen within the graft after 3 weeks, and to a slighter extent also after 1 year. Moreover, especially in grafts examined 3 weeks, but also 52 weeks, after transplantation, holes were observed in dilated capillary segments, suggesting that intussusceptive microvascular growth occurred in parallel with angiogenesis. A well-developed microvasculature could be observed 52 weeks after transplantation, whereas the number of capillaries in the implant was less pronounced 3 weeks postimplantation. The efferent venules were located peripherally in the islets and drained immediately into larger veins, derived from capsular veins clearly seen on the surface of the graft. It is concluded that xenotransplanted islet-like cell clusters develop an autonomous microcirculation by stimulating angiogenesis from surrounding blood vessels. Our findings suggest that single islet-like cell clusters remain morphologically intact after transplantation, and probably function as single endocrine units rather than forming a single homogenous endocrine tissue. Furthermore, it seems as if a continuous reorganization of the vasculature, with an associated angiogenesis, occurs throughout the observation period.