Graft vascular function after transplantation of pancreatic islets

Abstract

Endogenous pancreatic islets have a dense glomerular-like angioarchitecture, which ensures an optimal delivery of oxygen and nutrients to the islet cells, provides signals from other cells in the body and disposes secreted hormones. Transplantation of isolated islets means that their vascular connection is interrupted. The islet grafts therefore depend upon endothelial cells and microvessels originating in the implantation organ for derivation of a new vascular system. A re-establishment of islet blood-flow occurs within 7-14 days after transplantation, mainly through vascular sprouting. The newly formed blood vessels acquire the morphological characteristics of those in endogenous islets. In intraportally transplanted islets to the liver, the islets become revascularized almost exclusively from tributaries to the hepatic artery. Exocrine contamination of the transplanted islets could hamper the revascularization process, whereas neither cryopreservation nor immunosuppressive drugs like cyclosporin, prednisolon and RS-61443 have any essential effects on the angiogenesis. Investigators have noticed improvements in islet graft survival and function by means of basic fibroblast growth factor (bFGF), acidic FGF and endothelial cell growth factor exposure of the grafts. The functional properties of transplanted islets are largely unknown, but evidence from experimental islet transplantation suggests that both the blood perfusion and the tissue oxygen tension of the grafted islets are chronically decreased, indicating an insufficient vascular system. In order to achieve optimal condition for survival and function of transplanted beta cells, it is important to ascertain whether impairments in vascular function are present also after clinical islet transplantations as well.

Glucose and Endoplasmic Reticulum Calcium Channels Regulate HIF-1β via Presenilin in Pancreatic β-Cells

“…In addition, islet transplant failure is associated with hypoxia and related stresses during isolation, culture, and the post-transplantation period (39,40). In the present study, we show that blocking Ca 2ϩ flux from intracellular Ca 2ϩ channels induced the expression of HIF-1␤, a key member of the hypoxia-inducible factor family.…”

Cytocompatibility studies of mouse pancreatic islets on gelatin - PVP semi IPN scaffolds in vitro: Potential implication towards pancreatic tissue engineering

“…3 Loss of ECM proteins in the primary isolation of pancreatic islets, loss of cell-cell and cell-ECM interactions and disruption of microvasculature of the islets may cause islets to undergo apoptosis, and may result in the failure of the graft in the patient. 16,17 Therefore, the provision of a matrix that mediate cell adhesion and activate intracellular signaling pathways may be an important requirement for maintaining the function and viability of transplanted islets.…”

Evidence for a local angiotensin-generating system and dose-dependent inhibition of glucose-stimulated insulin release by angiotensin II in isolated pancreatic islets

“…However, its clinical application is severely restricted by the requirement of considerable number of islet cells [45,46], which might be due partly to a lack of proper engraftment thus leading to early graft failure [47]. A chronically low oxygen tension and a markedly decreased blood perfusion have been observed in transplanted islets [19,20,21].…”