Chen Shuang, Luo Jing, Shen Lanlin, Liu Xuan, Wang Wenshuang, Xu Jia, Ren Yushuang, Ye Yixin, Shi Gang, Cheng Fuyi, Cheng Lin, Su Xiaolan, Dai Lei, Gou Maling, Deng Hongxin
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
ACS Appl Mater Interfaces. 2022 May 11. doi: 10.1021/acsami.2c02487.
Transplantation of encapsulated islets has been shown to hold a promising potential treatment for type 1 diabetes (T1D). However, there are several obstacles to overcome, such as immune rejection by the host of the grafts, sustainability of islet function, and retrievability or replacement of the encapsulated system, hinder their clinical applications. In this study, mini-capsule devices containing islets were fabricated by using digital light processing (DLP) 3D printing. To ensure a high survival rate and low immunogenicity of the fabricated islets, 20s was selected as the most suitable printing condition. Meanwhile, the mini-capsule devices with a groove structure were fabricated to prevent islet cells leakage. Subcutaneous transplantations of encapsulated islets in immunocompetent C57BL/6 mice indicated significant improvement in the symptoms of streptozotocin-induced hyperglycemia without any immunosuppression treatment for at least 15 weeks. In vivo intraperitoneal glucose tolerance tests (IPGTT) performed at different time points demonstrated therapeutically relevant glycemic ameliorate of the device. The implants retrieved after 15 weeks still contained viable and adequate numbers of islet cells. The results of this study indicate that the proposed mini-capsule device can deliver sufficient islet cell mass, prevent islet cells leakage, and maintain long-term cell survival while allowing easy retrieval. Furthermore, the proposed encapsulated islets may help with T1D cellular treatment by overcoming the obstacles of islet transplantation.
封装胰岛移植已被证明对1型糖尿病（T1D）具有潜在的治疗前景。然而，仍有几个障碍需要克服，例如宿主对移植物的免疫排斥、胰岛功能的可持续性以及封装系统的可回收性或替换性，这些都阻碍了它们的临床应用。在本研究中，通过数字光处理（DLP）3D打印制造了含有胰岛的微型胶囊装置。为确保所制造胰岛的高存活率和低免疫原性，选择20秒作为最合适的打印条件。同时，制造了具有凹槽结构的微型胶囊装置以防止胰岛细胞泄漏。在免疫活性C57BL/6小鼠中进行皮下封装胰岛移植表明，在至少15周未进行任何免疫抑制治疗的情况下，链脲佐菌素诱导的高血糖症状有显著改善。在不同时间点进行的体内腹腔葡萄糖耐量试验（IPGTT）证明该装置具有治疗相关的血糖改善作用。15周后取出的植入物仍含有存活且数量充足的胰岛细胞。本研究结果表明，所提出的微型胶囊装置可以提供足够的胰岛细胞量，防止胰岛细胞泄漏，并维持细胞长期存活，同时便于取出。此外，所提出的封装胰岛可能通过克服胰岛移植的障碍来帮助进行T1D细胞治疗。
