A study of model beta-cells in Diabetes Treatment

模型β细胞在糖尿病治疗中的研究

• 批准号: 7150393
• 负责人: IOANNIS CONSTANTINIDIS
• 金额: $ 28.88万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-03-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7150393
• 关键词: alginates; artificial endocrine pancreas; bioengineering /biomedical engineering; biomaterial evaluation; biotechnology; laboratory mouse; medical implant science; method development; nuclear magnetic resonance spectroscopy; pancreatic islets; tissue engineering

DESCRIPTION (provided by applicant): The main criterion in assessing the therapeutic efficacy of tissue engineered construct is the successful restoration of the host's physiology. Direct and non-invasive in vivo monitoring of a construct is of great importance for the following reasons: it provides correlations between construct function and physiologic effects post-implantation in vivo; and it offers the possibility of assessing changes in construct function that may be used to develop early markers of construct failure in advance of the end-point effects. The overall objective of the proposed research is to develop a noninvasive methodology to monitor in vivo the function of an implanted tissue engineered pancreatic substitute. NMR is uniquely suited to perform such studies since it is a non-invasive modality that has the ability to probe into the intracellular metabolism of the construct, and to view the anatomy of the host at the site of implantation. NMR spectroscopic and imaging techniques can monitor several intracellular and extracellular metabolites without necessitating the introduction of foreign agents or the fixation of cells. It is our hypothesis that NMR detectable metabolic indexes can be used to monitor the function of an implanted tissue engineered pancreatic substitute and provide early indicators of implant failure while the recipient is still euglycemic. The NMR nuclei examined in this study include 1H, 19F and 31P, while the model pancreatic construct utilized is composed of mouse insulinoma #TC-tet cells or mouse islets encapsulated in alginate/poly-L- lysine/alginate beads and contained within an agarose matrix that allows for easy retrieval. The following Specific Aims are designed to address our hypothesis: Specific Aim 1: To optimize in vivo NMR signal acquisition with inductively coupled RF-coils. Specific Aim 2: To develop and validate a model of time-dependent oxygen and cell density gradients within constructs. Specific Aim 3: To non-invasively assess the function of an implanted tissue engineered pancreatic substitute and correlate that to end point physiologic events. We believe this to be a thorough, quantitative and a significant study to monitor the function of an implanted tissue engineered substitute that will identify metabolic events associated with failure ahead of its end physiologic effect. Proposed experiments are founded on strong preliminary data and we are confident that they will pave the way for further imaging studies in tissue engineering.

描述（由申请人提供）：评估组织工程结构的治疗功效的主要标准是宿主生理的成功恢复。由于以下原因，对构建体的直接和无创的体内监测非常重要：它在体内植入后构造功能与生理效应之间提供了相关性；它提供了评估构造功能变化的可能性，这些变化可用于在终点效应之前开发构造失败的早期标记。拟议的研究的总体目的是开发一种非侵入性方法来监测体内植入组织工程胰腺替代品的功能。 NMR非常适合进行此类研究，因为它是一种非侵入性形态，能够探测构建体的细胞内代谢，并在植入部位查看宿主的解剖结构。 NMR光谱和成像技术可以监测几种细胞内和细胞外代谢产物，而无需引入外国药物或细胞的固定。我们的假设是，NMR可检测的代谢指数可用于监测植入组织工程胰腺替代品的功能，并提供植入物衰竭的早期指标，而受体仍是尤利格血糖。这项研究中检查的NMR核包括1H，19F和31p，而所使用的模型胰腺构建体由小鼠胰岛素瘤＃TC-TET细胞或小鼠胰岛组成，或小鼠胰岛包裹在藻酸盐/聚-l-赖氨酸/藻酸盐/藻酸盐珠中，包含在琼脂糖基质中，可以易于恢复。以下特定目的旨在解决我们的假设：特定目的1：用电感耦合的RF-ails在体内NMR信号采集中进行优化。特定目的2：开发和验证构造中时间依赖性氧和细胞密度梯度的模型。特定目的3：非侵入性评估植入组织工程胰腺替代品的功能，并将其与终点生理事件相关联。我们认为，这是一项彻底，定量和一项重要的研究，以监测植入组织工程替代物的功能，该替代物将在其最终生理效应之前识别与失败相关的代谢事件。提出的实验建立在强大的初步数据上，我们相信它们将为组织工程的进一步成像研究铺平道路。