Designing a retrievable and scalable cell encapsulation device for potential treatment of type 1 diabetes
Designing a retrievable and scalable cell encapsulation device for potential treatment of type 1 diabetes
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DOI：
10.1073/pnas.1708806115
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发表时间：
2018-01-09
影响因子：
11.1
通讯作者：
Ma, Minglin
中科院分区：
文献类型：
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作者：
An, Duo;Chiu, Alan;Ma, Minglin
细胞包封已被证明有望有效、长期治疗1型糖尿病（T1D）。然而，其临床应用仍面临挑战。例如，有一种未满足的封装系统，能够提供足够的细胞质量，同时仍然允许方便的检索或替换。在这里，我们报告了一个简单的细胞封装设计，易于扩展和方便地检索。这种设计的关键是设计出一种高度可湿性的、释放Ca2+的纳米多孔聚合物线，这种线促进了均匀的原位交联，并在线周围形成了一层薄薄的海藻酸盐水凝胶。在短期（1个月）的研究中，该装置对免疫功能正常的C57BL/6小鼠的胰岛提供了类似于纯海藻酸盐纤维的免疫保护。然而，由于加强了中心螺纹，该装置的机械性能（对于处理和回收至关重要）比纯海藻酸盐纤维要坚固得多。扩散距离短，传质容易。我们通过使用大鼠胰岛对C57BL/6小鼠进行3个月的化学诱导糖尿病矫正，以及使用人胰岛对免疫缺陷SCID-Beige小鼠进行4个月的胰岛矫正，证明了该装置的治疗潜力。作为概念验证，我们进一步证明了该装置在狗身上的可扩展性和可重复性。在狗体内植入1个月后，该装置可以通过微创腹腔镜手术快速取出。这种封装装置可能有助于T1D的细胞治疗，因为它的可回收性和扩大的潜力。
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.