A prevascularized islet immunoisolation device

预血管化胰岛免疫隔离装置

• 批准号: 7596992
• 负责人: Stuart K Williams
• 金额: $ 31.45万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7596992
• 关键词: Address; Animal Model; Autologous; Beta Cell; Biocompatible Materials; Blood Circulation; Cell Survival; Cell Therapy; Cell Transplantation; Cell Transplants; Cell physiology; Cells; Chronic; Clinical; Clinical Trials; Collagen; Development; Devices; Diabetes Mellitus; Encapsulated; Endothelial Cells; Environment; Evaluation; Failure; Fatty acid glycerol esters; Gel; Generations; Goals; Graft Survival; Healed; Hybrids; Hyperglycemia; Immunosuppression; Insulin; Insulin-Dependent Diabetes Mellitus; Islet Cell; Islets of Langerhans; Islets of Langerhans Transplantation; Knowledge; Laboratories; Lead; Measurement; Metabolic; Methods; Microcirculation; Modification; Molecular; Morbidity - disease rate; Nutrient; Organ; Organ Transplantation; Patients; Perfusion; Pharmaceutical Preparations; Physiological; Postoperative Period; Recruitment Activity; Regional Perfusion; Replacement Therapy; Research; Research Personnel; Risk; Staging; Structure; Supporting Cell; Surface; System; Technology; Testing; Time; Tissue Engineering; Tissues; Transplantation; Vascular blood supply; Work; angiogenesis; base; beta cell replacement; design; diabetic; healing; implantation; improved; islet; mortality; mouse model; neovascularization; new technology; novel; pancreas allograft; response; yeast two hybrid system

DESCRIPTION (provided by applicant): Beta-cell replacement therapy via islet transplantation remains a promising technology for the reversal of type 1 diabetes. A significant barrier to the clinical utilization of beta cell transplants has been the lack of a host-derived blood supply to maintain the viability and thus the function of transplanted cells. We have developed a new cell-based therapy for the generation of pre-vascularized tissue engineered constructs. We have also developed a new generation of biomaterials that support extensive neovascularization. The combined cell and material construct to be evaluated is termed a Prevascularized Immuno-Isolation Device or PVID. We propose to use these materials in the development of a new beta-cell immuno-isolation device to prolong beta cell viability and function. These constructs represent a pre-formed microcirculation that can be constructed from a patient's own fat-derived microvascular endothelial cells, avoiding the use of immuno- suppressive drugs. Specific aim 1 will evaluate the maturation of the microcirculation within a prevascularized construct following implantation in an animal model. Specific aim 2 will evaluate novel porous biomaterials and material surface modification to support the neovascularization of the porous material to assure perfusion of encapsulated islets. The biomaterial developed is a two component hybrid system that also provides immunoisolation for the encapsulated islets. Specific aim 3 will evaluate the viability and function of islets encapsulated in the prevascularized immunoisolation devices in an animal model of diabetes.

描述（由申请人提供）：通过胰岛移植的β细胞替代疗法仍然是1型糖尿病逆转的有前途的技术。 beta细胞移植的临床利用的重要障碍是缺乏宿主衍生的血液供应来维持生存能力，从而维持移植细胞的功能。我们开发了一种新的基于细胞的疗法，用于生成血管前组织工程结构。我们还开发了新一代的生物材料，以支持广泛的新血管化。要评估的组合细胞和材料构建体称为前血管化免疫隔离装置或PVID。我们建议将这些材料用于开发新的β细胞免疫隔离装置来延长β细胞的生存能力和功能。这些构建体代表了预先形成的微循环，该微循环可以由患者自身的脂肪微血管内皮细胞构建，避免使用免疫抑制药物。特定的目标1将评估动物模型中植入后植入后的微循环的成熟。特定的目标2将评估新型的多孔生物材料和材料表面修饰，以支持多孔材料的新血管形成，以确保封装的胰岛灌注。开发的生物材料是两个组成杂种系统，还为封装的胰岛提供了免疫共透明。特定的目标3将评估糖尿病动物模型中封装在预胞浆免疫溶解装置中的胰岛的生存力和功能。