OPTIMIZATION OF PANCREAS FOR TRANSPLANTATION

优化胰腺移植

• 批准号: 2150343
• 负责人: HANS W SOLLINGER
• 金额: $ 19.5万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2150343
• 关键词: ABO(H) blood groups; MHC class I antigen; MHC class II antigen; cryopreservation; cryoprotective agents; diabetes mellitus therapy; embryo /fetus preservation; gene therapy; histocompatibility typing; human fetus tissue; insulin dependent diabetes mellitus; insulinlike growth factor; laboratory mouse; method development; pancreas transplantation; polymerase chain reaction; tissue /cell culture; tissue /organ preservation

Insulin-dependent diabetes mellitus (IDDM) is a disease that affects 1.4 million patients in the United States with an estimated health care cost of $14 billion annually. To date the only method which successfully frees the IDDM patient from insulin therapy and stabilizes or reverses the secondary complications of IDDM is vascularized pancreas transplantation. Because of the extreme shortage of donor organs, only 600 to 700 pancreas transplants are performed yearly. Transplantation with human fetal pancreas (HFP) is a technically simple procedure which offers many advantages for the treatment of IDDM including the potential for further growth and differentiation and readily available tissue. The objective of this proposal is to develop the standardized methods required to establish clinical HFP transplantation. This objective is defined as seven specific aims listed below. 1. development of standardized methods for the procurement and short-term storage of HFP. We will examine the media used for transplant and storage and determine the time constraints involved in HFP processing. 2. development of standardized methods for detecting bacterial, fungal, and viral contaminants of HFP. We will identify bacterial and fungal contaminants using standard techniques and identify viral contaminants with PCR. 3. Determination of the optimum method for HFP cryopreservation. We will examine several parameters of cryopreservation and determine the optimum post-processing stage for freezing. 4. Correlation of HFP in vitro function with in vivo function. We propose experiments to correlate in vitro function with in vivo function to successfully predict the ability of HFP to reverse diabetes. 5. Development of techniques to accelerate HFP maturation and in vivo function. We will use both cell culture and gene therapy approaches to assess the effects of insulin-like growth factors on the maturation of HFP. 6. Determination of the optimum HFP transplant site. We will compare the renal subcapsular site with other sites that provide portal drainage and are surgically simple. 7. Development of standardized methods for HLA typing of HFP. We propose experiments to adapt serological techniques to type for class I and PCR techniques to type for class II.

胰岛素依赖型糖尿病（IDDM）是一种影响1.4 在美国，估计有100万名患者的医疗保健费用 每年140亿美元。 迄今为止，唯一成功的方法 使胰岛素依赖型糖尿病患者免于胰岛素治疗， 继发性并发症是血管化胰腺 移植 由于捐献器官极度短缺，只有 每年进行600至700例胰腺移植。 移植 人胎儿胰腺（HFP）是一种技术上简单的程序， 为治疗胰岛素依赖型糖尿病提供了许多优势， 用于进一步生长和分化以及容易获得的组织。 的 这项建议的目的是制定标准化的方法， 需要建立临床HFP移植。 这一目标 具体分为以下七个目标。 1. 发展 采购和短期储存HFP的标准化方法。 我们将检查用于移植和储存的培养基， 处理HFP的时间限制。 2. 发展 检测细菌、真菌和病毒的标准化方法 污染的HFP。 我们将鉴定细菌和真菌污染物 使用标准技术并通过PCR鉴定病毒污染物。 3. HFP冻存最佳方法的确定。 我们将 检查冷冻保存的几个参数并确定最佳参数 冷冻后处理阶段。 4. 体外HFP相关性 功能与体内功能。 我们提出实验， 体外功能与体内功能成功预测的能力 来逆转糖尿病。 5. 开发技术以加速 HFP成熟和体内功能。 我们将使用细胞培养和 评估胰岛素样生长效应的基因治疗方法 影响HFP成熟的因素。 6. 最佳HFP的确定 移植部位 我们将比较肾包膜下部位与其他部位 提供门静脉引流且手术简单的部位。 7. HFPHLA分型标准化方法的建立 我们提出 使血清学技术适应I类和PCR分型的实验 技术类型为第二类。