Nyitray Crystal E, Chang Ryan, Faleo Gaetano, Lance Kevin D, Bernards Daniel A, Tang Qizhi, Desai Tejal A
∥Department of Surgery, University of California, San Francisco, 513 Parnassus Avenue HSE520 Box 0780, San Francisco, California 94143, United States.
ACS Nano. 2015 Jun 23;9(6):5675-82. doi: 10.1021/acsnano.5b00679. Epub 2015 May 14.
Cell-encapsulating devices can play an important role in advancing the types of tissue available for transplantation and further improving transplant success rates. To have an effective device, encapsulated cells must remain viable, respond to external stimulus, and be protected from immune responses, and the device itself must elicit a minimal foreign body response. To address these challenges, we developed a micro- and a nanoporous thin-film cell encapsulation device from polycaprolactone (PCL), a material previously used in FDA-approved biomedical devices. The thin-film device construct allows long-term bioluminescent transfer imaging, which can be used for monitoring cell viability and device tracking. The ability to tune the microporous and nanoporous membrane allows selective protection from immune cell invasion and cytokine-mediated cell death in vitro, all while maintaining typical cell function, as demonstrated by encapsulated cells' insulin production in response to glucose stimulation. To demonstrate the ability to track, visualize, and monitor the viability of cells encapsulated in implanted thin-film devices, we encapsulated and implanted luciferase-positive MIN6 cells in allogeneic mouse models for up to 90 days. Lack of foreign body response in combination with rapid neovascularization around the device shows promise in using this technology for cell encapsulation. These devices can help elucidate the metrics required for cell encapsulation success and direct future immune-isolation therapies.
细胞封装装置在增加可用于移植的组织类型以及进一步提高移植成功率方面可以发挥重要作用。为了拥有有效的装置,封装的细胞必须保持存活,对外部刺激作出反应,并免受免疫反应的影响,而且装置本身必须引发最小的异物反应。为了应对这些挑战,我们用聚己内酯(PCL)开发了一种微孔和纳米孔薄膜细胞封装装置,PCL是一种先前用于获得美国食品药品监督管理局批准的生物医学装置的材料。薄膜装置结构允许进行长期生物发光转移成像,可用于监测细胞活力和装置追踪。调节微孔和纳米孔膜的能力可在体外选择性地保护细胞免受免疫细胞侵袭和细胞因子介导的细胞死亡,同时保持典型的细胞功能,如封装细胞在葡萄糖刺激下产生胰岛素所证明的那样。为了证明追踪、可视化和监测植入薄膜装置中封装细胞活力的能力,我们在同种异体小鼠模型中封装并植入了荧光素酶阳性的MIN6细胞,长达90天。缺乏异物反应以及装置周围快速的新生血管形成表明该技术在细胞封装方面具有应用前景。这些装置有助于阐明细胞封装成功所需的指标,并指导未来的免疫隔离疗法。