Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, People's Republic of China.
Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology, Chongqing Medical University, Chongqing 400016, People's Republic of China.
Drug Des Devel Ther. 2020 Sep 29;14:4021-4027. doi: 10.2147/DDDT.S273050. eCollection 2020.
Islet transplantation is regarded as the most promising treatment for type 1 diabetes (T1D). However, the function of grafted islet could be damaged on account of transplant rejection and/or hypoxia several years later after transplantation. We proposed a hypothetical functionalized hydrogel model, which encapsulates sufficient A20 high-expressing islets and supporting cells, and performs as a drug release system releasing immunosuppressants and growth factors, to improve the outcome of pancreatic islet transplantation. Once injected in vivo, the hydrogel can gel and offer a robust mechanical structure for the A20 high-expressing islets and supporting cells. The natural biomaterials (eg, heparin) added into the hydrogel provide adhesive sites for islets to promote islets' survival. Furthermore, the hydrogel encapsulates various supporting cells, which can facilitate the vascularization and/or prevent the immune system attacking the islet graft. Based on the previous studies that generally applied one or two combined strategies to protect the function of islet graft, we designed this hypothetical multifunctional encapsulation hydrogel model with various functions. We hypothesized that the islet graft could survive and maintain its function for a longer time in vivo compared with naked islets. This hypothetical model has a limitation in terms of clinical application. Future development work will focus on verifying the function and safety of this hypothetical islet transplantation hydrogel model in vitro and in vivo.
胰岛移植被认为是治疗 1 型糖尿病（T1D）最有前途的方法。然而，移植后数年，移植物的功能可能会因移植排斥和/或缺氧而受损。我们提出了一个假设的功能化水凝胶模型，该模型包封了足够数量的高表达 A20 的胰岛和支持细胞，并作为一种药物释放系统释放免疫抑制剂和生长因子，以改善胰岛移植的效果。一旦在体内注射，水凝胶可以凝胶并为高表达 A20 的胰岛和支持细胞提供强大的机械结构。添加到水凝胶中的天然生物材料（例如肝素）为胰岛提供了附着点，以促进胰岛的存活。此外，水凝胶包封了各种支持细胞，这可以促进血管生成和/或防止免疫系统攻击胰岛移植物。基于先前的研究通常应用一种或两种联合策略来保护胰岛移植物的功能，我们设计了这个具有多种功能的假设多功能包封水凝胶模型。我们假设与裸胰岛相比，胰岛移植物在体内能够存活更长时间并保持其功能。这个假设模型在临床应用方面存在局限性。未来的发展工作将集中在体外和体内验证这个假设的胰岛移植水凝胶模型的功能和安全性。
