SUCCESSFUL REVERSAL OF SPONTANEOUS DIABETES IN DOGS BY INTRAPERITONEAL MICROENCAPSULATED ISLETS
SUCCESSFUL REVERSAL OF SPONTANEOUS DIABETES IN DOGS BY INTRAPERITONEAL MICROENCAPSULATED ISLETS
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DOI：
10.1097/00007890-199211000-00001
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发表时间：
1992-11-01
期刊：
影响因子：
6.2
通讯作者：
LEE, M
中科院分区：
文献类型：
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作者：
SOONSHIONG, P;FELDMAN, E;LEE, M
在糖尿病大型动物模型中，通过微囊化胰岛的腹膜内移植的长期存活尚未被描述。在这项研究中，我们报告了通过这种方法在自发性糖尿病犬中成功地长期逆转糖尿病。我们已经确定了与基于藻酸盐的微胶囊纤维化相关的基本机制，并设计了改善该问题的方法。这些包括使用低甘露糖醛酸含量的纯化藻酸盐和细胞因子抑制。将10只胰岛素依赖性自发性糖尿病犬（胰岛素需求量1 - 4单位/kg/天;不存在循环C肽且糖尿病K值为0.6 +/-0.4）纳入研究。分离来自杂种供体胰腺的胰岛并将其作为游离胰岛对照（n = 3）或作为微囊化胰岛同种异体移植物（n = 7）腹膜内移植。在所有7个包封的胰岛接受者中，在24小时内达到了正常血糖（血清葡萄糖从304 +/-117降至116 +/-72 mg/dl）。胰岛移植后14天进行的IVGTT显示K值从移植前的0.6 +/-0.4变为2.6 +/-0.6。所有接受包封胰岛的动物在63 - 172天的时间内保持血糖正常，不需要外源性胰岛素，中位胰岛素依赖性为105天。相比之下，接受游离胰岛的受体在植入后7天内排斥移植物。总之，这是第一次报告的长期成功逆转自发性糖尿病的大型动物模型，腹腔注射囊化胰岛。这种形式的治疗在治疗人类I型糖尿病中存在潜力。
Long-term euglycemia by intraperitoneal transplantation of microencapsulated islets has not been described in the diabetic large animal model. In this study, we report the successful long-term reversal of diabetes by this method in spontaneous diabetic dogs. We have identified fundamental mechanism(s) associated with alginate-based microcapsule fibrosis, and have devised methods to ameliorate this problem. These include the use of purified alginate of low mannuronic acid content and cytokine suppression. Ten insulin-dependent, spontaneous diabetic dogs (insulin requirement 1-4 units/kg/day; absence of circulating C-peptide and diabetic K-values of 0.6+/-0.4) were entered into the study. Islets from mongrel donor pancreata were isolated and transplanted intraperitoneally either as free islet controls (n=3) or as microencapsulated islet allografts (n=7). In all seven encapsulated islet recipients, euglycemia was achieved within 24 hr (serum glucose falling from 304+/-117 to 116+/-72 mg/dl). IVGTT performed 14 days after islet transplant demonstrated normalization of K-values changing from a pretransplant level of 0.6+/-0.4 to 2.6+/-0.6. All animals receiving encapsulated islets remained euglycemic, free of the need for exogenous insulin, for a period of 63-172 days, with a median insulin-independence for 105 days. In contrast, recipients receiving free islets rejected their graft within seven days of implantation. In conclusion, this is the first report of long-term successful reversal of spontaneous diabetes in the large animal model by an intraperitoneal injection of encapsulated islets. The potential exists for this form of therapy to be explored in the treatment of type I diabetes in man.