基于高分子球形包囊的免疫隔离装置制备及人工胰腺的皮下移植研究

Type I diabetes (T1D) is a chronic autoimmune condition, which is also one of the most common severe chronic illnesses diagnosed in children and young adults. In recent years, protocols have been established to generate insulin-secreting human pancreatic beta cells from stem cells. The availability of the stem cell-derived beta cells (SC-βC) then opened opportunities for cell replacement therapy for treating T1D. However, hurdles remain as to how to overcome host immune reactions and provide vascularized environment to accommodate the transplanted cells in the body. Here, we propose to investigate the fabrication of spherical polymer-based immunoisolation membrane with advanced structural and functional characteristics. The new devices will be having controllable encapsulation volume and super-thin immunoselective stuctures, thereby to transform the current devices by improving the transport and mechanical properties. The new polymer-based spherical immunoisolation devices will be used to build SC-βC-based artificial pancreas modules. A transplantation strategy will also be investigated to understand how to transplant pancreas modules into fat-removed superficial fascia in subcutaneous space. The project will lead to the development of SC-βC-based devices that are suitable for implantation, retrieval and replacement in the clinical setting for treating T1D. The investigation will also develop new systems and generate new theories for fields of biomaterials and regenerative medicine.

1型糖尿病（Type I diabetes, T1D）是严重威胁人类健康的一种慢性自身免疫疾病。近年来干细胞技术已可获得分泌胰岛素的胰腺β细胞（stem cell-derived β cell, SC-βC），有望为T1D治疗带来划时代的细胞替代治疗方法。而SC-βC或者胰岛移植需要克服宿主免疫反应并获得丰富血供，以保障移植细胞的活性和功能。本项目拟针对糖尿病细胞替代治疗亟待解决的临床问题，加工以高分子材料为基础的球囊形免疫隔离装置。将通过先进加工方法，研制具有可控装载体积和超薄免疫隔离厚度的新一代植入型装置，并突破传统免疫隔离装置加工方法对材料、传质结构及力学性能的局限性。课题还将构建SC-βC人工胰腺模块，研究结合脂肪移除、在皮下浅筋膜组织内植入人工胰腺。基于高分子材料的球囊形免疫隔离装置的研制有望开发出可植入、取出和更换的人工胰腺，并发展生物医用材料的新技术和细胞替代治疗的新途径。

本课题结合多孔支架设计与半透膜制备，通过设计材料的微纳米结构、可控复合水凝胶，研究了新型胰岛免疫隔离装置的构建原理和制造技术，以及异体异种细胞递送后替代受损细胞功能的有效性。研究工作中，我们致力于设计结构丰富且确定的多孔薄膜材料，降低材料/细胞体积比，减少包囊物质交换屏障的厚度，改善传质。课题已获得球形、平面型和图案化三类包囊装置，并在动物模型中开展了异体和异种胰岛移植研究。课题开发装置在降低细胞移植的免疫排异、提高受体对移植体的耐受性应用中有进一步研究前景。