PANCREATIC TRANSPLANTATION AND DIABETES MELLITUS

胰腺移植和糖尿病

• 批准号: 2137789
• 负责人: DANIEL H MINTZ
• 金额: $ 27.17万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-05-01 至 1996-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2137789
• 关键词: FK506; autologous transplantation; clinical biomedical equipment; cyclosporines; dendritic cells; density gradient ultracentrifugation; diabetes mellitus; diabetes mellitus therapy; dogs; helper T lymphocyte; histochemistry /cytochemistry; histocompatibility; human subject; humoral immunity; immunosuppression; immunotherapy; immunotoxicity; isoantigen; laboratory mouse; lymphocyte proliferation; macrophage; monoclonal antibody; pancreatectomy; pancreatic islet transplantation; radiotracer; suppressor T lymphocyte; tissue /cell culture; tissue /cell preparation

Further refinements in the technique we currently use to isolate human islets are proposed. The procedure will test several solutions constructed to stabilize cells during collagenase digestion, and will introduce a hydroclone device to facilitate bulk separation of liquid from solids in the final digestion slurp. We will continue to modify a special centrifuge that will have capacity sufficiently large to hold the total digestion slurp in a discontinuous gradient composed of Eurocollins-Ficoll and/or Eurocollins-Albumin. The-gradient will be emptied by activating a hydraulic system that permits the key gradient layers to be harvested directly into a sterile plastic bag that is used to infuse the islet preparations. Clinical transplantation trials, already initiated, will be expanded and the effects on islet allograft survival of several different immunosuppression regimens will be compared. We will also generate a series of canine monoclonal antibodies directed against canine dendritic cells and 'macrophages, as well as to T cell subsets. CD4 and CD8 peptides will be synthesized based on sequence analysis data obtained from cloned cDNAs which encode these canine lymphocyte antigens. The peptides will be used to generate anti-CD4 and anti-CD8 MoAbs. The anti-dendritic cell and anti-macrophage MoAbs will be used to immunomodulate canine islets, in vitro. The anti-CD4 and anti-CD8 MoAbs will be used for recipient immunotherapy, alone, in combinations, and in association with low dose cyclosporine or FK506. Dogs with pancreatectomy-induced diabetes will be used to evaluate the potential value of deletion of CD4 and/or CD8 T cells in vivo for immunosuppression and/or tolerization to islet allografts.

我们目前使用的分离技术的进一步改进 人类的小岛被提出了。该程序将测试几个 胶原酶期间为稳定细胞而构建的溶液 消化，并将引入水力旋流装置，以方便 在最终消化过程中液体与固体的整体分离 发出咕噜声。我们将继续改装一台特殊的离心机， 有足够大的容量来容纳总的消化液 在由Eurocollins-Ficoll和/或 Eurocollins-白蛋白。将通过激活一个 液压系统，允许关键梯度层 直接放入无菌塑料袋中，用于 注入胰岛制剂。临床移植试验， 已经启动，将扩展并对小岛产生影响 几种不同免疫抑制方案对同种异体移植物存活的影响 将会被比较。我们还将产生一系列的犬科动物 针对犬树突状细胞和 巨噬细胞，以及T细胞亚群。CD4和CD8多肽 将根据从以下来源获得的序列分析数据进行合成 克隆了编码这些犬类淋巴细胞抗原的cDNA。这个 多肽将被用来产生抗CD4和抗CD8的MoAb. 抗树突状细胞和抗巨噬细胞MoAbs将用于 免疫调节犬胰岛，体外实验。抗CD4和抗CD8抗体 年，MoAbbs将单独用于接受者免疫治疗 联合用药，并与低剂量环孢素或 FK506。患有胰腺切除所致糖尿病的狗将被用来 评估CD4和/或CD8 T细胞缺失的潜在价值 体内对胰岛的免疫抑制和/或耐受 异体移植。