Laboratory of Organ and Tissue Reconstruction, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
Biotechnol Bioeng. 2018 Sep;115(9):2341-2355. doi: 10.1002/bit.26730. Epub 2018 Jun 6.
Transplantation of encapsulated porcine islets is proposed to treat type 1 diabetes. However, the envelopment of fibrous tissue and the infiltration of immune cells impair islet function and eventually cause implant failure. It is known that hemodialysis using an ethylene vinyl alcohol (EVOH) membrane results in minor tissue responses. Therefore, we hypothesized that using a low-adhesive EVOH membrane for encapsulation may prevent host cell accumulation and fibrous capsule formation. In this study, rat islets suspended in chitosan gel were encapsulated in bags made from highly porous EVOH membranes, and their in vitro insulin secretion function as well as in vivo performance was evaluated. The results showed that the EVOH bag did not affect islet survival or glucose-stimulated insulin secretion. Whereas naked islets were dysfunctional after 7 days of culture in vitro, islets within the EVOH bag produced insulin continuously for 30 days. Streptozotocin-induced diabetic mice were given islets-chitosan gel-EVOH implants intraperitoneally (650-800 islets equivalent) and exhibited lower blood glucose levels and regained body weight during a 4-week observation period. The transplanted mice had higher levels of serum insulin and C-peptide, with an improved blood glucose disappearance rate. Retrieved implants had minor tissue adhesion, and histology showed a limited number of mononuclear cells and fibroblasts surrounding the implants. No invasion of host cells into the EVOH bags was noticed, and the encapsulated islets were intact and positive for insulin-glucagon immunostaining. In conclusion, an EVOH bag can protect encapsulated islets, limit fibrous capsule formation, and extend graft function.
将猪胰岛包封移植被提议用于治疗 1 型糖尿病。然而，纤维组织的包绕和免疫细胞的浸润会损害胰岛功能，最终导致移植物失功。已知使用乙烯-乙烯醇（EVOH）膜进行血液透析会引起轻微的组织反应。因此，我们假设使用低黏附性的 EVOH 膜进行包封可能会防止宿主细胞聚集和纤维囊形成。在这项研究中，悬浮在壳聚糖凝胶中的大鼠胰岛被包封在由高多孔 EVOH 膜制成的袋子中，并评估了它们的体外胰岛素分泌功能和体内性能。结果表明，EVOH 袋不会影响胰岛的存活或葡萄糖刺激的胰岛素分泌。虽然裸胰岛在体外培养 7 天后功能失调，但 EVOH 袋内的胰岛持续产生胰岛素 30 天。链脲佐菌素诱导的糖尿病小鼠经腹腔内给予胰岛-壳聚糖凝胶-EVOH 植入物（650-800 个胰岛当量），在 4 周的观察期内表现出血糖水平降低和体重恢复。移植的小鼠具有更高水平的血清胰岛素和 C 肽，血糖清除率得到改善。取出的植入物仅有轻微的组织黏附，组织学显示植入物周围有少量单核细胞和成纤维细胞。未发现宿主细胞侵入 EVOH 袋中，包封的胰岛完整且胰岛素-胰高血糖素免疫染色阳性。总之，EVOH 袋可以保护包封的胰岛，限制纤维囊形成，并延长移植物功能。
