NPC/islet cotransplantation and colocalization prevents allograft rejection.

Diabetic Balb/c mice were transplanted under the kidney capsule with 350 EI purified from C57BL/6 mice. Mice were not treated (Islet-Tx, n = 12) or treated with rapamycin plus FK506 plus anti–IL-2Rα mAb (Edmonton-Tx, n = 26), or co-transplanted with NPC (1,000 neurospheres) under the same kidney of the islets (Co-NPC-Tx, n = 10) or under the controlateral one (NPC-Tx, n = 7). Gray area: all diabetic Balb/c mice that were transplanted 100 days before with C57BL/6 islets were challenged with donor-derived splenocytes. Left Panel: Kaplan-Meier Analysis for the graft survival between the four groups of recipients. Hundred days after transplantation there was a significant difference between Edmonton-Tx and Islet-Tx or between Co-NPC-Tx and Islet-Tx. In contrast, there was no statistical significant difference between NPC-Tx and Islet-Tx. In all cases, the graft survival was monitored by glycemia levels. A graft was considered rejected when glycemia was >300 mg/dl for two consecutive measurement. *P<0.05 and **P<0.01 vs. Islet-Tx, Log Rank-Kaplan-Meier analysis. Right Panel: not fasting blood glucose profile of Islet-Tx and Co-NPC-Tx after receiving islets. Data are expressed as mean (line) and ±1 standard error (area). ^a Statistical analysis was performed by tests of repeated measures ANOVA considering two intervals: from 0 to 100 days (before donor-derived splenocytes boost) and from day 100 to day 140 (after donor-derived splenocytes boost). * p<0.05; ** p<0.01.