Biological and Environmental Engineering, Cornell University, Ithaca, NY, 14853, USA.
Department of Clinical Sciences, Cornell University, Ithaca, NY, 14853, USA.
Adv Mater. 2019 Dec;31(52):e1905135. doi: 10.1002/adma.201905135. Epub 2019 Nov 11.
Cell replacement therapy is emerging as a promising treatment platform for many endocrine disorders and hormone deficiency diseases. The survival of cells within delivery devices is, however, often limited due to low oxygen levels in common transplantation sites. Additionally, replacing implanted devices at the end of the graft lifetime is often unfeasible and, where possible, generally requires invasive surgical procedures. Here, the design and testing of a modular transcutaneous biphasic (BP) cell delivery device that provides enhanced and unlimited oxygen supply by direct contact with the atmosphere is presented. Critically, the cell delivery unit is demountable from the fixed components of the device, allowing for surgery-free refilling of the therapeutic cells. Mass transfer studies show significantly improved performance of the BP device in comparison to subcutaneous controls. The device is also tested for islet encapsulation in an immunocompetent diabetes rodent model. Robust cell survival and diabetes correction is observed following a rat-to-mouse xenograft. Lastly, nonsurgical cell refilling is demonstrated in dogs. These studies show the feasibility of this novel device for cell replacement therapies.
细胞替代疗法作为一种有前途的治疗平台，正在被应用于许多内分泌紊乱和激素缺乏疾病的治疗中。然而，由于常见移植部位的氧气含量低，输送装置内的细胞存活率通常较低。此外，在移植物寿命结束时更换植入设备通常是不可行的，而且在可行的情况下，通常需要进行侵入性手术。在这里，设计并测试了一种模块化的经皮双相（BP）细胞输送装置，该装置通过与大气直接接触提供增强和无限的氧气供应。关键的是，细胞输送单元可从设备的固定组件上拆卸下来，从而可以在无需手术的情况下重新填充治疗细胞。与皮下对照相比，传质研究表明 BP 装置的性能有了显著提高。该装置还在免疫活性糖尿病啮齿动物模型中进行了胰岛包封测试。在大鼠到小鼠异种移植后观察到了稳健的细胞存活和糖尿病纠正。最后，在犬中进行了非手术细胞再填充的演示。这些研究表明了这种新型装置在细胞替代疗法中的可行性。
