A Safe, Fibrosis-Mitigating, and Scalable Encapsulation Device Supports Long-Term Function of Insulin-Producing Cells.
A Safe, Fibrosis-Mitigating, and Scalable Encapsulation Device Supports Long-Term Function of Insulin-Producing Cells.
复制标题
DOI：
10.1002/smll.202104899
复制
发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Ma M
中科院分区：
文献类型：
--
作者：
Liu W;Flanders JA;Wang LH;Liu Q;Bowers DT;Wang K;Chiu A;Wang X;Ernst AU;Shariati K;Caserto JS;Parker B;Gao D;Plesser MD;Grunnet LG;Rescan C;Pimentel Carletto R;Winkel L;Melero-Martin JM;Ma M
胰岛素产生细胞的包裹和移植为治疗1型糖尿病(T1D)提供了一种前景光明的治疗方法，而不需要免疫抑制。然而，用于包裹细胞的生物材料经常会引起异物反应，导致细胞过度生长和纤维组织沉积，这反过来又减少了与移植细胞的质量传递。同时，封装设备必须是安全的、可伸缩的、理想的可回收的，以满足临床需求。在这里，我们报告了一种耐用且安全的纳米纤维装置，它涂覆了一种薄而均匀的、减轻纤维化、两性离子修饰的藻酸盐水凝胶，用于包裹胰岛和干细胞衍生的β细胞(SC-β)。我们设计了一种将细胞封装在圆柱壁内的配置，允许在不牺牲传质的情况下在径向和纵向进行放大。由于其易于传质和低水平的纤维化反应，该设备支持长期细胞植入，在C57BL6/J小鼠中使用大鼠胰岛可纠正长达399天的糖尿病，在SCID米色小鼠中使用人SC-β细胞可纠正长达238天的糖尿病。我们进一步在狗身上展示了可伸缩性和可检索性。这些结果表明，这种新的细胞疗法在治疗T1D和其他疾病方面具有潜力。开发了一种安全、低免疫反应、胰岛包裹、长期功能装置(SHIELD)，用于运送胰岛和人SC-β细胞。Shield具有同心配置和由两性离子修饰的海藻酸盐制成的薄、均匀、减轻纤维化、耐用的水凝胶涂层，可伸缩、可回收并在糖尿病小鼠中实现长达399天的正常血糖，显示出用于1型糖尿病的无免疫抑制细胞疗法的前景。
Encapsulation and transplantation of insulin-producing cells offer a promising curative treatment for type 1 diabetes (T1D) without immunosuppression. However, biomaterials used to encapsulate cells often elicit foreign body responses, leading to cellular overgrowth and deposition of fibrotic tissue, which in turn diminishes mass transfer to and from transplanted cells. Meanwhile, the encapsulation device must be safe, scalable, and ideally retrievable to meet clinical requirements. Here we report a durable and safe nanofibrous device coated with a thin and uniform, fibrosis-mitigating, zwitterionically modified alginate hydrogel for encapsulation of islets and stem cell-derived beta (SC-β) cells. We designed the device with a configuration that has cells encapsulated within the cylindrical wall, allowing scale-up in both radial and longitudinal directions without sacrificing mass transfer. Due to its facile mass transfer and low level of fibrotic reactions, the device supported long-term cell engraftment, correcting diabetes in C57BL6/J mice with rat islets for up to 399 days and SCID-beige mice with human SC-β cells for up to 238 days. We further demonstrated the scalability and retrievability in dogs. These results suggest the potential of this new device for cell therapies to treat T1D and other diseases. A Safe, Hypo-immunoreactive, Islet Encapsulation, Long-term-functional Device (SHIELD) is developed to deliver islets and human SC-β cells. The SHIELD, featuring a concentric configuration and a thin, uniform, fibrosis-mitigating, durable hydrogel coating of zwitterionically modified alginate, is scalable, retrievable and achieved normoglycemia in diabetic mice for up to 399 days, showing promise for immunosuppression-free cell therapies for type 1 diabetes.
登录
查看更多内容
影响因子：
28.1
作者：
Bose S;Volpatti LR;Thiono D;Yesilyurt V;McGladrigan C;Tang Y;Facklam A;Wang A;Jhunjhunwala S;Veiseh O;Hollister-Lock J;Bhattacharya C;Weir GC;Greiner DL;Langer R;Anderson DG
通讯作者：
Anderson DG
DOI：
10.1073/pnas.1708806115
发表时间：
2018-01-09
影响因子：
11.1
作者：
An, Duo;Chiu, Alan;Ma, Minglin
通讯作者：
Ma, Minglin
影响因子：
3.3
作者：
Barkai, Uriel;Weir, Gordon C.;Rotem, Avi
通讯作者：
Rotem, Avi
影响因子：
2.2
作者：
Ludwig, B.;Zimerman, B.;Barkai, U.
通讯作者：
Barkai, U.
影响因子：
6.2
作者：
Ladd, Jon;Zhang, Zheng;Jiang, Shaoyi
通讯作者：
Jiang, Shaoyi