Yong Cai, Wang Zhengxin, Zhang Xing, Shi Xiaomin, Ni Zhijia, Fu Hong, Ding Guoshan, Fu Zhiren, Yin Hao
Department of Transplantation, First Affiliated Hospital of Wenzhou Medical College, Wenzhou, People's Republic of China.
Department of Surgery, Organ Transplant Center, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China.
Int J Nanomedicine. 2014 Feb 17;9:985-93. doi: 10.2147/IJN.S55812. eCollection 2014.
Here, we investigated in diabetic mice the therapeutic effect of monocyte chemoattractant protein-1 (MCP-1), locally delivered by an electrospun scaffold, on transplanted islets. This therapeutic scheme is expected to exert a synergistic effect to ameliorate hyperglycemia and its associated nephrotic disorders. The cumulative amount of MCP-1 released from the scaffold in vitro within a 3-week window was 267.77 ± 32.18 ng, without a compromise in bioactivity. After 8 weeks following the transplantation, the islet population stimulated by MCP-1 was 35.14%± 7.23% larger than the non-stimulated islet population. Moreover, MCP-1 increased concentrations of blood insulin and C-peptide 2 by 49.83%± 5.29% and 43.49%± 9.21%, respectively. Consequently, the blood glucose concentration in the MCP-1 group was significantly lower than that in the control group at week 2 post-surgery. MCP-1 also enhanced the tolerance of sudden oral glucose challenge. The rapid decrease of blood creatinine, urine creatinine, and blood urea nitrogen suggested that the recovery of renal functions compromised by hyperglycemia could also be attributed to MCP-1. Our study shed new light on a synergistic strategy to alleviate hyperglycemia and nephrotic disorders in diabetic patients.
在此,我们在糖尿病小鼠中研究了通过电纺支架局部递送的单核细胞趋化蛋白-1(MCP-1)对移植胰岛的治疗效果。这种治疗方案有望发挥协同作用,改善高血糖及其相关的肾病。在3周的时间窗口内,支架在体外释放的MCP-1累积量为267.77±32.18 ng,且生物活性未受影响。移植后8周,受MCP-1刺激的胰岛数量比未受刺激的胰岛数量多35.14%±7.23%。此外,MCP-1使血液中胰岛素和C肽的浓度分别增加了49.83%±5.29%和43.49%±9.21%。因此,在术后第2周,MCP-1组的血糖浓度显著低于对照组。MCP-1还增强了对突然口服葡萄糖挑战的耐受性。血肌酐、尿肌酐和血尿素氮的快速下降表明,高血糖损害的肾功能恢复也可归因于MCP-1。我们的研究为缓解糖尿病患者高血糖和肾病的协同策略提供了新的思路。