Matrigel basement membrane matrix significantly enhances graft function of subcutaneously transplanted allogenic murine islets

Objectives: The subcutaneous (SC) site has been approached as an alternative for islet transplant studies but has met with limited success mainly because of poor vascular supply to the graft. Matrigel basement membrane matrix (MATRIGEL) has been successfully used to grow mammalian cells SC in SCID mice. MATRIGEL, a solubilized basement membrane preparation extracted from mouse sarcoma, is rich in angiogenic growth factors and provides a physiologically favorable environment for the grafted tissue. Therefore, we hypothesized that MATRIGEL would be suitable for islets transplanted SC and be an attractive alternative for in vivo islet function analysis. Methods: C57BL/6 mice were used as islet donors and CD-1 mice as recipients. Streptozotocin was used to induce diabetes by single IP injection of 250mg/kg body weight. 600 islets were injected SC into the scruff region of the neck (with or without MATRIGEL) or transplanted (without MATRIGEL) surgically under the kidney capsule (KC). Posttransplant, NFBG levels were monitored with tail-vein blood for 28 days. Furthermore, after 21 days an intraperitoneal glucose tolerance test (IPGTT) was performed. After 28 days the grafts were retrieved for histology. Results: It was quite impressive to note that the SC transplantation of MATRIGEL embedded islets leads in 8 of 10 recipients to rapid and constant normoglycemia. In contrast, without matrigel normoglycemia could be achieved only in 1 of 10 SC-grafts. Angiogenesis was significantly enhanced in MATRIGEL-grafts. Importantly, glucose clearance kinetics of matrigel embedded islets during IPGTT differ not from islets transplanted under the kidney capsule (KC). Conclusions: In summary, this study indicates that SC transplantation of islets in MATRIGEL can restore normoglycemia in CD-mice. This is a simple model for studying islet function and that has several advantages over the conventional method of transplantation under the KC. The mechanism by which MATRIGEL results in rapid normoglycemia is most likely caused by enhanced angiogenesis.