OPTIMIZATION OF PANCREAS FOR TRANSPLANTATION

胰岛素依赖型糖尿病是一种影响1.4的疾病 美国有100万名患者，估计医疗保健费用 每年140亿美元。到目前为止，唯一一种成功 使IDDM患者从胰岛素治疗中解脱出来，稳定或逆转 IDDM的继发并发症是带血管的胰腺 移植。由于捐献器官的极度短缺，只有 每年要进行600到700例胰腺移植。移植 人胎儿胰腺移植(HFP)是一种技术上简单的程序， 为IDDM的治疗提供了许多优势，包括潜在的 以进一步生长和分化，并随时获得组织。这个 本提案的目标是开发标准化方法 需要建立临床HFP移植。这个目标是 定义为以下列出的七个具体目标。1.发展 HFP的采购和短期储存的标准化方法。 我们将检查用于移植和存储的介质，并确定 HFP处理过程中涉及的时间限制。2.发展 检测细菌、真菌和病毒的标准化方法 HFP的污染物。我们将确定细菌和真菌污染物 使用标准技术，并用聚合酶链式反应鉴定病毒污染物。3. HFP冷冻保存最佳方法的确定。我们会 考察超低温保存的几个参数，确定最佳超低温保存条件 冷冻的后处理阶段。4.HFP的体外相关性 具有体内功能的功能。我们建议进行相关的实验 体外功能与体内功能成功预测能力 HFP来逆转糖尿病。5.加速技术的发展 HFP的成熟和体内功能。我们将同时使用细胞培养和 评估胰岛素样生长效应的基因治疗方法 影响HFP成熟度的因素。6.最佳HFP的确定 移植地点。我们将比较肾被膜下部位与其他部位 提供门户引流和手术操作简单的站点。7. HFP人类白细胞抗原分型标准化方法的建立我们建议 使血清学技术适应I类和聚合酶链式反应分型的实验 二班打字技巧。

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.