Revascularization and remodelling of pancreatic islets grafted under the kidney capsule

Abstract

The revascularization and the structural changes resulting from interactions between the graft and the host were investigated in transplanted pancreatic islets under the kidney capsule. Islets were isolated from mice pancreata and transplanted in syngeneic diabetic animals. Graft-bearing kidneys were collected on different days posttransplant and processed for light microscopy, immunohistochemistry and transmission electron microscopy. A numerical analysis was performed in order to compare the percentage number of the different types of cells in native islets and at different time points after the transplant. Recipient animals reversed diabetes within 4 days.An intraperitoneal glucose tolerance test was performed to determine islet functionality under stressful conditions.During the initial few days post-transplant, the islets showed peculiar shapes and the graft tended to aggregate along the vessels. Starting at days 4 -7 post-transplant, islets were revascularized from vessels connected to both the cortical and the capsular vascular network of the kidney. From day 7-14 post-transplant, the vessels progressively appeared more similar in features and size to those of in situ pancreatic islets. Both the percentage number of the different cell types and the distribution of Alpha, Beta and Delta cells inside the graft were significantly different as compared with intact islets, demonstrating quantitative and structural changes after the engraftment. No concomitant proliferation of Beta cells was detected using a bromodeoxyuridin staining method. Despite the fact that quick revascularization preserved a large mass of tissue, the remodelling process of the graft and the newly formed vascularization led to a different organization of the endocrine tissue as compared with intact in situ islets. This constitutes the morphological basis for alterations of the normal intercellular interactions and may explain the altered secretory cell function often observed in transplant.

Implanted islets in the anterior chamber of the eye are prone to autoimmune attack in a mouse model of diabetes

“…2). It is well established that islets transplanted under the kidney capsule become highly vascularised [27]. Islet grafts within the anterior chamber became highly vascularised within several days of transplantation, generally via a large vessel running through the transplanted area with many small branches supplying different graft regions (ESM Video 1).…”

Pancreatic Islet Transplantation Using Vascularised Chambers Containing Nerve Growth Factor Ameliorates Hyperglycaemia in Diabetic Mice

“…The diabetic rats demonstrated a return to normoglycaemic levels that was maintained for more than 160 days. Islet transplantation under the kidney capsule [Morini et al, 2007], epididymal fat pad [Chen et al, 2007] and spleen [Gustavson et al, 2005] have been successful in reversing diabetes in rodents. However, these sites are not ideal in the clinical setting.…”

Collagen IV-Modified Scaffolds Improve Islet Survival and Function and Reduce Time to Euglycemia

“…16 The engraftment and function of transplanted islets can be impaired by the isolation process that severs critical vascular connections and disrupts interactions between islet cells and their ECM. [18][19][20][21][22][23][24][25][26][27] These interactions regulate many aspects of islet physiology, including survival, proliferation, and insulin secretion. 15,23,28 Reconstruction of islet cell-ECM relationships following isolation mitigates the loss of differentiated islet structure and function, reduces apoptosis and necrosis of b-cells, 29 and increases insulin secretion.…”