SURVIVAL AND FUNCTION OF PURIFIED ISLETS IN THE OMENTAL POUCH SITE OF OUTBRED DOGS
SURVIVAL AND FUNCTION OF PURIFIED ISLETS IN THE OMENTAL POUCH SITE OF OUTBRED DOGS
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DOI：
10.1097/00007890-199309000-00007
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发表时间：
1993-09-01
期刊：
影响因子：
6.2
通讯作者：
WARNOCK, GL
中科院分区：
文献类型：
--
作者：
AO, ZL;MATAYOSHI, K;WARNOCK, GL
本研究的目的是设计一个网膜袋网站胰岛植入在临床前的大型动物，并比较胰岛移植到这个网站的功能与胰岛植入脾脏。从远系杂种狗中分离高度纯化的胰岛，然后移植到完全切除胰腺的远系受体中。将自体胰岛移植物植入大网膜袋（组[gp] 1，n=12）或通过静脉回流植入脾脏（组[gp] 2，n=12）。将单个供体胰岛的同种异体移植物植入接受CsA（n=9）或未治疗对照（n=3）的狗的网膜袋（gp 3）中。在gp 1中持续逆转糖尿病的阈值胰岛质量为10穆尔/kg，超过gp 2所需的2.5倍。在6只gp 1和8只gp 2犬中诱导并维持了2个月的正常代谢。IVGTT时，gp 1的K值（葡萄糖下降，%/min）为1.3 ± 0.4，gp 2为1.5 ± 0.2（P>0.2）。外周静脉胰岛素水平显着降低（P 10穆尔/kg），最初血糖正常：未处理对照组的移植物在4.2+/-1.8天失败。在1只CsA治疗的狗中，移植物由于技术原因失败;在其他8只狗中，正常的免疫力持续了10、15和21天，在5只狗中持续了>30天。当CsA治疗在第30天停止时，正常持续34+/-9.5天。我们的结论是，纯化的胰岛移植到糖尿病狗的网膜袋后恢复正常。与脾内胰岛移植相比，需要增加移植物体积，且胰岛素水平较低。
The aims of this study were to devise an omental pouch site for islet implantation in a preclinical large animal and to compare the function of islets engrafted to this site with islets implanted into the spleen. Highly purified islets were isolated from outbred mongrel dogs, then grafted into totally pancreatectomized outbred recipients. Autografts of islets were implanted into a greater omental pouch (group [gp] 1, n=12) or into the spleen by venous reflux (gp 2, n=12). Allografts of single donor islets were implanted into the omental pouch (gp 3) of dogs that received CsA (n=9) or untreated controls (n=3). The threshold islet mass that consistently reversed diabetes in gp 1 was 10 mul/kg, which exceeded by 2.5-fold that required in gp 2. Normoglycemia was induced and maintained for 2 months in 6 gp 1 and 8 gp 2 dogs. At IVGTT, the K value (decline in glucose, %/min) was 1.3+/-0.4 in gp 1 versus 1.5+/-0.2 in gp 2 (P>0.2). Peripheral venous insulin levels were significantly lower (P 10 mul/kg) were initially normoglycemic: grafts of untreated controls failed at 4.2+/-1.8 days. In 1 CsA-treated dog the graft failed for technical reasons; normoglycemia persisted in the other 8 for 10, 15, and 21 days, and in 5 instances for >30 days. When CsA therapy was stopped at 30 days, normoglycemia persisted for 34+/-9.5 days. We conclude that purified islets restore normoglycemia after implantation into the omental pouch of diabetic dogs. Compared with intrasplenic islet implantation, an increased graft volume is required and insulin levels are lower.