Effects of pre-vascularization of tissue-engineered constructs on the survival of transplanted pancreaticislets / 中国组织工程研究

ABSTRACT

BACKGROUND:Pancreatic islet transplantationviaportal vein system leads to the apoptsis of a number of islet cels due to local hypoxia,therebyaffecting transplant outcomes. OBJECTIVE:To explore theeffect ofpre-micrvascularization network of tissue-engineered constructs on the survival of transplanted islets and the feasibility of xenogenic islet transplantation. METHODS:A 5-mm-long cylindrical silicone tube filed with Matrigel TM matrix surrounding the superficial epigastric vessel was placed in the groin ofdiabetic mice. After the syngeneic islets with 300 islet equivalents (IEQ) were transplanted into the silicone chamber on days 0, 14 and 28 post-chamber implantation, respectively, the recovery time of blood glucose was observed. The islets with the quantity of 100 IEQ, 200 IEQ and 300 IEQ, respectively, were transplanted on day 28 post-implantation and then the blood glucoselevelwas determined. Moreover, the survival of human pancreatic islets with 1 000 IEQ transplanted into the pre-vascularizated chamber or under the renal capsule of diabetic mice, folowed by the treatment of anti-CD45RB and/or anti-CD40L (MR-1) was analyzed. RESULTS AND CONCLUSION:An abundant micro-vascularized network was established in the silicone chamber on day 28 post-implantation. The time of the blood glucose returningto normal level in diabetic mice was negatively correlated with the time required for pre-vascularization and the number of implanted islets. No islet grafts implanted in the silicone chamber and treated by anti-CD45RB survived for long term. However, one of seven (14.3%) grafts survived for long term, which was not significantly different from the transplantation under the renal capsule group (n=8, MST > 71 days,P> 0.05). The tissue-engineered pre-vascularization network markedly extends the survival time of the islet grafts before transplantation. The transplantation of the xenogenic pancreatic islets into the vascularized silicone chamber might be a promising method in the future clinical application.