PURIFIED CANINE ISLET AUTOGRAFTS - FUNCTIONAL OUTCOME AS INFLUENCED BY ISLET NUMBER AND IMPLANTATION SITE

PURIFIED CANINE ISLET AUTOGRAFTS - FUNCTIONAL OUTCOME AS INFLUENCED BY ISLET NUMBER AND IMPLANTATION SITE
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DOI:
10.1097/00007890-199009000-00006
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发表时间:
1990-09-01
期刊:
影响因子:
6.2
通讯作者:
SUTHERLAND, DER
SUTHERLAND, DER
中科院分区:
医学2区
文献类型:
--
作者:
KAUFMAN, DB;MOREL, P;SUTHERLAND, DER

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使用胰腺导管内胶原酶消化和密度梯度纯化分离犬胰岛的基本原理的修改,结合同时荧光和双硫腙胰岛染色,我们量化了分离的胰岛的产量,纯度和活力。然后,我们确定了总的和重量校正的胰岛计数和植入部位对纯化的犬胰岛自体移植物的即时和长期功能结果的综合影响。重量校正的胰岛计数在区分成功和不成功的胰岛自体移植物植入胰腺切除犬的肝脏(n = 10)和脾脏(n = 10)方面具有100%的敏感性和特异性。在肝脏(4400个胰岛/kg)和脾脏(4650个胰岛/kg)中达到正常血糖所需的胰岛阈值数量几乎相同。当以4400至5500个胰岛/kg的计数植入肾包膜下间隙(n = 5)时,胰岛自体移植物未能改善高血糖症。用纯化的胰岛自体移植物移植到肝脏的狗的平均1个月和3个月静脉内葡萄糖耐量试验K值(-1.43 . ±. 0.27和-1.69 .+-。0.27)和脾(-1.78 . ±. 0.36和-1.64 .+-。0.3)也是相似的。然而,对于肝内胰岛,达到正常血糖所需的时间显著缩短(P < 0.02)(1.0 ± 0.01)。0.0移植后30天)比脾内胰岛(6.8 ±. 2.3移植后天数)。胰岛自体移植功能的长期耐久性不是无限的。总的来说,13个犬胰岛自体移植受体在移植后被跟踪≥ 12个月(范围12-18个月),7个犬胰岛自体移植受体(5个肝内受体和2个脾内受体)分别在2、6、11、13、14、8和16个月时自发复发高血糖症。这种现象只取决于植入的胰岛数量。这些数据强调了定量定义的胰岛制备的意义以及胰岛数量和植入部位对犬胰岛自体移植物的即时和长期功能结果的重要性。
Using a modification of the basic principles of pancreatic intraductal collagenase digestion and density gradient purification to isolate canine islets, in conjunction with simultaneous fluorogenic and dithizone islet staining, we quantified the yield, purity, and viability of the isolated islets. We then determined the combined influences of total and weight-corrected islet counts and implantation site on immediate and long-term functional outcome of purified canine islet autografts. Weight-corrected islet counts were 100% sensitive and specific in differentiating successful and unsuccessful islet autografts implanted to the liver (n = 10) and spleen (n = 10) of pancreatectomized dogs. The threshold number of islets required to achieve normoglycemia in the liver (4400 islets/kg) and spleen (4650 islets/kg) were nearly identical. Islet autografts failed to ameliorate hyperglycemia when implanted to the renal subcapsular space (n = 5) at counts of 4400 to 5500 islets/kg. The mean one- and three-month intravenous glucose tolerance test K-values of dogs with purified islet autografts to the liver (-1.43 .+-. 0.27 and -1.69 .+-. 0.27, respectively) and spleen (-1.78 .+-. 0.36 and -1.64 .+-. 0.3, respectively) were also similar. Time needed to achieve normoglycemia, however, was significantly (P < 0.02) shorter for intrahepatic islets (1.0 .+-. 0.0 days posttransplant) than intrasplenic islets (6.8 .+-. 2.3 days posttransplant). The long-term durability of islet autograft function was not unlimited. Overall, thirteen canine islet autograft recipients have been followed for .gtoreq.12 months posttransplant (range 12-18 months), seven canine islet autograft recipients (five intrahepatic and two intrasplenic) have had spontaneous recurrence of hyperglycemia at 2, 6, 11, 13, 14, 8, and 16 months, respectively. The phenomenon depended only on the number of islets implanted. The data underscore the significance of quantitatively defined islet preparations and the importance of islet number and implantation site on immediate and long-term functional outcome of canine islet autografts.