Improving Cell Encapsulation by Detection and Mitigation of Protruding Cells

1型糖尿病患者需要终生每天注射胰岛素。移植分泌胰岛素的β型细胞是一种很有前景的治疗策略，它需要为移植细胞提供充足的氧气和营养，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公司已经开发出专有的植入式Cell PouchTM设备技术，该设备可以血管化，然后可以装载胰岛细胞、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裹在300微米的海藻酸钙珠中来提供，但这种方法现在已知会导致一些细胞从胶囊表面突出，从而影响整个移植。外海藻酸钙外壳被添加到突出的细胞，但这使终珠直径增加了一倍，不可接受地增加了死亡体积，降低了胰岛素分泌能力。因此，需要新的策略来检测细胞突出，并形成具有更小死亡体积的外壳。Stöver在设计和评估海藻酸盐为基础的胶囊细胞疗法的专业知识。在这个项目中，他的团队将开发新的三维荧光定量检测突出细胞，并探索低死体积双包封的范围。这些信息将为未来的胶囊成分和形态提供信息，以优化细胞保护和遏制以及细胞功能。

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.