A prevascularized islet immunoisolation device

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逆转1型糖尿病的一项有前途的技术。临床应用β细胞移植的一个重要障碍是缺乏宿主来源的血液供应来维持移植细胞的活力和功能。我们已经开发了一种新的基于细胞的治疗方法，用于生成预血管化组织工程结构。我们还开发了支持广泛新生血管的新一代生物材料。要评估的细胞和材料组合结构称为预血管化免疫隔离装置或PVID。我们建议将这些材料用于开发一种新的β细胞免疫隔离装置，以延长β细胞的活力和功能。这些结构代表了预先形成的微循环，可以从患者自己的脂肪来源的微血管内皮细胞构建，避免使用免疫抑制药物。具体目的1将在动物模型植入后评估预血管化结构内微循环的成熟情况。具体目标2将评估新型多孔生物材料和材料表面修饰，以支持多孔材料的新血管化，以确保被包裹的胰岛的灌注。所开发的生物材料是一种双组分杂交系统，也为被封装的胰岛提供免疫隔离。具体目的3将评估胰岛包封在预血管化免疫隔离装置在糖尿病动物模型中的生存能力和功能。

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.