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Designing a retrievable and scalable cell encapsulation device for potential treatment of type 1 diabetes
Proceedings of the National Academy of Sciences of the United States of America ( IF 11.1 ) Pub Date : 2018-01-09 00:00:00 , DOI: 10.1073/pnas.1708806115
Duo An 1 , Alan Chiu 1 , James A. Flanders 2 , Wei Song 1 , Dahua Shou 3 , Yen-Chun Lu 1 , Lars G. Grunnet 4 , Louise Winkel 4 , Camilla Ingvorsen 4 , Nicolaj Strøyer Christophersen 4 , Johannes Josef Fels 5 , Fredrik Wolfhagen Sand 4 , Yewei Ji 6 , Ling Qi 6 , Yehudah Pardo 7 , Dan Luo 1, 8, 9 , Meredith Silberstein 10 , Jintu Fan 3 , Minglin Ma 1
Affiliation  

Cell encapsulation has been shown to hold promise for effective, long-term treatment of type 1 diabetes (T1D). However, challenges remain for its clinical applications. For example, there is an unmet need for an encapsulation system that is capable of delivering sufficient cell mass while still allowing convenient retrieval or replacement. Here, we report a simple cell encapsulation design that is readily scalable and conveniently retrievable. The key to this design was to engineer a highly wettable, Ca2+-releasing nanoporous polymer thread that promoted uniform in situ cross-linking and strong adhesion of a thin layer of alginate hydrogel around the thread. The device provided immunoprotection of rat islets in immunocompetent C57BL/6 mice in a short-term (1-mo) study, similar to neat alginate fibers. However, the mechanical property of the device, critical for handling and retrieval, was much more robust than the neat alginate fibers due to the reinforcement of the central thread. It also had facile mass transfer due to the short diffusion distance. We demonstrated the therapeutic potential of the device through the correction of chemically induced diabetes in C57BL/6 mice using rat islets for 3 mo as well as in immunodeficient SCID-Beige mice using human islets for 4 mo. We further showed, as a proof of concept, the scalability and retrievability in dogs. After 1 mo of implantation in dogs, the device could be rapidly retrieved through a minimally invasive laparoscopic procedure. This encapsulation device may contribute to a cellular therapy for T1D because of its retrievability and scale-up potential.

中文翻译:

设计可回收和可扩展的细胞封装设备,以治疗1型糖尿病

细胞封装已显示出对有效,长期治疗1型糖尿病(T1D)的希望。然而,其临床应用仍然面临挑战。例如,对于能够提供足够的细胞质量同时仍允许方便的取回或替换的封装系统存在未满足的需求。在这里,我们报告了一个简单的单元封装设计,该设计易于扩展且可方便地检索。该设计的关键是设计出高度可润湿的Ca 2+的纳米多孔聚合物线,可促进均匀的原位交联并增强线周围海藻酸盐水凝胶薄层的牢固附着力。该设备在短期(1-mo)研究中为具有免疫能力的C57BL / 6小鼠的大鼠胰岛提供了免疫保护,类似于纯藻酸盐纤维。但是,由于中心线的增强,对于机械操作和回收至关重要的设备的机械性能比纯藻酸盐纤维坚固得多。由于扩散距离短,它也易于传质。我们通过校正使用大鼠胰岛3个月的C57BL / 6小鼠以及使用人类胰岛4个月的免疫缺陷SCID-Beige小鼠,通过校正化学诱导的糖尿病证明了该设备的治疗潜力。我们进一步证明,作为概念证明,狗的可扩展性和可检索性。在狗体内植入1个月后,可以通过微创腹腔镜手术迅速恢复该设备。由于其可回收性和规模化潜力,该封装设备可能有助于T1D的细胞疗法。
更新日期:2018-01-10
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