2.0000
#9-OR
DEVELOPMENT OF A UNIQUE IN VIVO MURINE MODEL TO STUDY ISLET ENGRAFTMENT AND FUNCTION.
A. Bharat, MBBS, N. Benshoff, S. Ramachandran, PhD, N. Desai, MD and T. Mohanakumar, PhD. Washington U Surg and St. Louis MO, USA, Washington U, Path.

---

Introduction: Islet transplantation under kidney capsule (KC) in diabetic SCID (d-SCID) mice is the standard for in vivo islet function studies. However, poor neovascularization at this site leads to inconsistent islet function. Besides, this procedure is technically demanding and associated with significant animal mortality. Matrigel basement membrane matrix (MM), rich in angiogenic factors, is known to enhance neovascularisation. The goal of this study was to test if MM would be optimal for subcutaneous(s/c) islet transplantation.
Methodology: Streptozotocin (200mg/kg, single IP) was used to induce diabetes (non-fasting blood glucose [NFBG] > 300mg/dl) in SCID mice. 3000 human islet equivalents (HIE) were either injected s/c with MM or transplanted under KC. NFBG was monitored for 30 days following which grafts were retrieved. Similarly, 3000 porcine islet equivalents (PIE) were injected s/c with MM into d-SCID mice.
Results : Seven of 9 mice in MM and 7 of 10 in KC group achieved normoglycemia (NFBG<150 mg/dl) with 3000 HIE. MM group revealed NFBG control much earlier (mean 3.4 days Vs 5.3, p=0.03). All 7 recipients of 3000 PIE with MM achieved rapid normoglycemia. Upon graft removal, the animals became hyperglycemic again. Histology showed presence of discrete islets with well-preserved architecture and numerous blood vessels in the MM. In contrast, islets under KC appeared clumped and encroaching the renal parenchyma with no discernible vessels developing into the graft.
Conclusions: Islets transplanted s/c with MM can restore normoglycemia. This model is an attractive alternate to KC transplantation and provides a unique opportunity to study islet engraftment since MM can be easily reconstituted with cytokines and growth factors.