Improving Cell Encapsulation by Detection and Mitigation of Protruding Cells

1型糖尿病患者需要终身每天注射胰岛素。移植分泌胰岛素的β型细胞是一种很有前途的治疗策略，需要为移植细胞提供良好的氧气和营养，以及对移植细胞的有效免疫保护，并防止细胞从胶囊中逃逸。Sernova公司开发了专有的植入式Cell PouchTM设备技术，该设备经过血管化处理，然后可以装载胰岛，β细胞或其他治疗细胞。Cell PouchTM中的免疫保护可以通过将这些细胞包封在300微米的藻酸钙珠中来提供，但是现在已知这种方法会导致一些细胞突出胶囊表面，损害整个移植物。已经添加了外部藻酸钙壳来包覆突出的细胞，但这使最终珠直径加倍，不可接受地增加了死体积并降低了胰岛素分泌能力。因此，需要新的策略来检测细胞突起，并形成具有较低死体积的外壳。Stöver博士在设计和评估用于细胞治疗的藻酸盐胶囊方面具有专业知识。在这个项目中，他的团队将开发新的突出细胞的3D定量荧光分析，并探索具有较低死体积的双循环的范围。这些信息将为未来的胶囊成分和形态提供信息，以优化细胞保护和容纳以及细胞功能。

Type 1 diabetics require daily insulin injections for life. Transplanting insulin-secreting beta-type cells is apromising therapeutic strategy that requires an excellent supply of oxygen and nutrients to the transplantedcells, as well as effective immune protection of the transplanted cells, and prevention of cells escaping fromcapsules.Sernova Corp has developed proprietary implantable Cell PouchTM device technologies that becomevascularized and can then be loaded with islets, beta cells or other therapeutic cells. Immunoprotection in theCell PouchTM can be provided by encapsulating these cells in 300 micrometer calcium alginate beads, but thisapproach is now known to lead to some cells protruding through the capsule surfaces, compromising the wholetransplant. Outer calcium alginate shells have been added to coat protruding cells, but this doubles the finalbead diameter, unacceptably increasing dead volume and decreasing insulin secretion capacity. New strategiesfor detecting cell protrusion, and for forming outer shells with lower dead volume, are hence needed.Dr. Stöver has expertise in design and evaluation of alginate-based capsules for cell therapies. In this project,his group will develop new 3D quantitative fluorescence assays for protruding cells, and explore the scope fordouble encapsulations with lower dead volume. This information will inform future capsule compositions andmorphologies, in order to optimize cell protection and containment as well as cell function.