Xu J, Miao G, Zhao Y, Wei J
Department of General Surgery, Beijing Hospital, Beijing, China.
Transplant Proc. 2011 Nov;43(9):3205-8. doi: 10.1016/j.transproceed.2011.09.058.
Synthetic extracellular matrix (ECM) has been shown to be efficient to preserve the function of transplanted islets. In this study using a mouse model, we sought to determine whether subcutaneous transplantation was a convenient procedure for achieving normoglycemia.
We performed in vitro tests as well as morphologic observations and Western blotting to establish that embedded islets survived better than non-embedded islets. Streptozotocin-induced diabetic mice (BALB/c) were transplanted with ECM-embedded syngeneic islets via the subcutaneous (SC; n = 5) or subrenal capsule (SRC; n = 6) routes. We measured mean blood glucose levels at various points from pretransplantation to postoperative day 14, and examined immunohistochemistry staining for insulin in the transplant grafts on day 14.
Islets transplanted with ECM gel retained better structure and developed a functional vasculature. Western blotting showed more caspase-3 expressed in the non-embedded islets, which indicated more islet cells undergoing apoptosis. On the first day after transplantation, glucose levels were significantly decreased in the SRC group compared with the SC group: 383.33 ± 44.50 mg/dL to 80.67 ± 16.85 mg/dL versus 414.00 ± 92.33 mg/dL to 278.28 ± 121.80 mg/dL (P < .05). Glucose levels were better maintained in the SRC group than the SC group over 14 days. Immunohistochemistry staining for insulin showed fewer islets in the SC group.
Embedded islets with ECM gel functioned better than non-embedded ones in vitro. However, the subcutaneous route may not be an ideal site for islet transplantation.
合成细胞外基质(ECM)已被证明能有效保留移植胰岛的功能。在本研究中,我们使用小鼠模型,试图确定皮下移植是否是实现正常血糖水平的便捷方法。
我们进行了体外试验以及形态学观察和蛋白质印迹法,以证实包埋的胰岛比未包埋的胰岛存活得更好。将链脲佐菌素诱导的糖尿病小鼠(BALB/c)通过皮下(SC;n = 5)或肾被膜下(SRC;n = 6)途径移植包埋于ECM中的同基因胰岛。我们在从移植前到术后第14天的不同时间点测量平均血糖水平,并在第14天检查移植移植物中胰岛素的免疫组织化学染色。
用ECM凝胶移植的胰岛保留了更好的结构并形成了功能性脉管系统。蛋白质印迹法显示未包埋的胰岛中表达更多的半胱天冬酶-3,这表明更多的胰岛细胞正在经历凋亡。移植后第一天,SRC组的血糖水平与SC组相比显著降低:从383.33±44.50mg/dL降至80.67±16.85mg/dL,而SC组从414.00±92.33mg/dL降至278.28±121.80mg/dL(P <.05)。在14天内,SRC组的血糖水平比SC组维持得更好。胰岛素免疫组织化学染色显示SC组的胰岛较少。
在体外,用ECM凝胶包埋的胰岛比未包埋的胰岛功能更好。然而,皮下途径可能不是胰岛移植的理想部位。