Rivereau A S, Darquy S, Chaillous L, Maugendre S, Gouin E, Reach G, Sai P
Laboratory of Cellular and Molecular Immuno-Endocrinology, INRA/ENVN, University School of Medicine, Nantes, France.
Diabetes Metab. 1997 Jun;23(3):205-12.
Intraperitoneal xenografting of islets immunoprotected by semipermeable membranes is a potential method of avoiding rejection by reversal of diabetes without immunosuppression. In this preliminary study, a xenograft of porcine islets, immunoprotected in semipermeable hollow fibres composed of a hydrogel of a polyacrylonitrile-sodium methallylsulphonate copolymer (AN 69), was used to reverse autoimmune insulin-dependent diabetes mellitus (IDDM) in the NOD mouse. A diabetic state was maintained in all 46 NOD mice which received transplants of empty fibres. Transplantation of encapsulated islets reversed the diabetic state in 37% (18/54) of the recipients. In these mice, nonfasting blood glucose concentration decreased within 24 h. Glycaemia was kept below the diabetic control range and the initial pretransplant value for 6 weeks. Recipient NOD mice suffered from the severe insulitis characteristic of clinical diabetes, confirming that reversal of the hyperglycaemic state was due solely to the xenografts. Pretransplant glycaemia was slightly (p < 0.05) higher in mice which remained diabetic after grafts of fibre-containing islets than in animals which experienced reversal of hyperglycaemia after transplantation) for the peritoneal cavity of recipients which had returned to normoglycaemia after grafting with islet-containing fibres. In all 4 cases, the islets responded to glucose during a perifusion assay. In 2 out of 4 grafts removed from mice which remained hyperglycaemic after grafting with islet-containing fibres (11, 13, 15 and 27 days after transplantation), no basal or stimulated insulin secretion was detectable. Histological sections of a total of 75 fibres retrieved from the peritoneal cavities of recipient NOD mice showed surrounding inflammation, with adherent cells, neovascularisation and fibrotic reaction. These preliminary results are promising for the continued development of this bioartificial pancreas for xenogeneic islet transplantation since they demonstrate that xenogeneic islets can survive in the autoimmune environment of the NOD mouse with spontaneous diabetes mimicking human IDDM).
通过半透膜免疫保护的胰岛进行腹腔异种移植是一种在不进行免疫抑制的情况下逆转糖尿病从而避免排斥反应的潜在方法。在这项初步研究中，将猪胰岛在由聚丙烯腈 - 甲基烯丙基磺酸钠共聚物（AN 69）水凝胶构成的半透性中空纤维中进行免疫保护后进行异种移植，用于逆转非肥胖糖尿病（NOD）小鼠的自身免疫性胰岛素依赖型糖尿病（IDDM）。所有46只接受空纤维移植的NOD小鼠均维持糖尿病状态。移植包封的胰岛使37%（18/54）的受体糖尿病状态得到逆转。在这些小鼠中，非空腹血糖浓度在24小时内下降。血糖水平在6周内维持在糖尿病对照范围以下及移植前初始值以下。受体NOD小鼠患有临床糖尿病特有的严重胰岛炎，证实高血糖状态的逆转完全归因于异种移植。移植含胰岛纤维后仍患糖尿病的小鼠移植前血糖水平略高于移植后高血糖状态逆转的动物（对于移植含胰岛纤维后恢复正常血糖的受体腹腔而言）。在所有4例中，胰岛在灌注试验中对葡萄糖有反应。在移植含胰岛纤维后仍高血糖的小鼠体内取出的4个移植物中的2个（移植后11、13、15和27天），未检测到基础或刺激后的胰岛素分泌。从受体NOD小鼠腹腔中总共取出75根纤维的组织学切片显示周围有炎症，伴有黏附细胞、新生血管形成和纤维化反应。这些初步结果对于这种用于异种胰岛移植的生物人工胰腺的持续开发很有前景，因为它们表明异种胰岛能够在模拟人类IDDM的自发性糖尿病NOD小鼠的自身免疫环境中存活。
