Improving Cell Encapsulation by Detection and Mitigation of Protruding Cells

通过检测和减轻突出细胞来改善细胞封装

• 批准号: 509228-2017
• 负责人: Stöver, Harald
• 金额: $ 1.82万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Engage Grants Program
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=639941
• 关键词: Improving; Cell; Encapsulation; Detection; Mitigation

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.

1型糖尿病患者终生需要每日注射胰岛素。移植分泌胰岛素的β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，并防止细胞从包膜中逃脱。Sernova公司开发了专有的植入性Cell PouchTM设备技术，该设备可以被血管化，然后可以装载胰岛、β细胞或其他治疗性细胞。在Cell PouchTM中，可以通过将这些细胞包裹在300微米的海藻酸钙微珠中来提供免疫保护，但现在已知这种方法会导致一些细胞从胶囊表面突出，影响整个移植。海藻酸钙外壳被添加到突出细胞的外套中，但这会使最终直径加倍，不可接受地增加死亡体积并降低胰岛素分泌能力。因此，需要新的策略来检测细胞突起，并形成具有较低死区体积的外壳。施托弗在细胞疗法的海藻酸盐胶囊的设计和评估方面拥有专业知识。在这个项目中，他的团队将为突起的细胞开发新的3D定量荧光分析，并探索具有更低死亡体积的双重包膜的范围。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。