A prevascularized islet immunoisolation device

描述（由申请人提供）：通过胰岛移植进行的 β 细胞替代疗法仍然是逆转 1 型糖尿病的一项有前景的技术。 β细胞移植临床应用的一个重大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。我们开发了一种新的基于细胞的疗法，用于生成预血管化的组织工程构建体。我们还开发了支持广泛新生血管形成的新一代生物材料。待评估的组合细胞和材料构建体称为预血管化免疫隔离装置或PVID。我们建议使用这些材料开发新型 β 细胞免疫隔离装置，以延长 β 细胞的活力和功能。这些构建体代表了预先形成的微循环，可以由患者自身的脂肪来源的微血管内皮细胞构建，从而避免使用免疫抑制药物。具体目标 1 将评估植入动物模型后预血管化结构内微循环的成熟程度。具体目标 2 将评估新型多孔生物材料和材料表面改性，以支持多孔材料的新血管形成，从而确保封装胰岛的灌注。开发的生物材料是一种两组分混合系统，还为封装的胰岛提供免疫隔离。具体目标 3 将评估糖尿病动物模型中封装在预血管化免疫隔离装置中的胰岛的活力和功能。

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.