PANCREATIC TRANSPLANTATION AND DIABETES MELLITUS

胰腺移植和糖尿病

• 批准号: 3227599
• 负责人: DANIEL H MINTZ
• 金额: $ 63.61万
• 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 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3227599
• 关键词: 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.

进一步改进我们目前用来分离 提出了人类胰岛。 该程序将测试几个 构建用于在胶原酶作用期间稳定细胞的溶液 消化，并将引入水力旋流器装置，以促进 在最终消化中液体与固体的大量分离 咕噜咕噜。 我们将继续改进一种特殊的离心机， 具有足够大的容量以容纳全部消化浆液 在由Eurocollins-Ficoll和/或 Eurocolins-白蛋白。 梯度将通过激活 液压系统，允许关键梯度层， 直接收获到无菌塑料袋中， 注入胰岛制剂 临床移植试验， 已经开始，将扩大和对胰岛的影响， 几种不同免疫抑制方案对同种异体移植物存活的影响 将被比较。 我们还将生成一系列犬科动物 针对犬树突细胞的单克隆抗体， 巨噬细胞以及T细胞亚群。 CD 4和CD 8肽 将基于从以下获得的序列分析数据合成： 克隆的编码这些犬淋巴细胞抗原的cDNA。 的 肽将用于产生抗CD 4和抗CD 8单克隆抗体。 抗树突状细胞和抗巨噬细胞单克隆抗体将用于 免疫调节犬胰岛，体外。 抗CD 4和抗CD 8 单克隆抗体将单独用于受体免疫治疗， 联合用药，并与低剂量环孢菌素或 FK506 患有胰腺切除术诱导的糖尿病的犬将用于 评估CD 4和/或CD 8 T细胞缺失的潜在价值 在体内用于对胰岛免疫抑制和/或耐受 同种异体移植