Wang Ziqiang, Li Ya, Sun Chenxuan, Cui Pukong, Han Yuanyuan, Wu Tong, Xu Bai, Zhang Can, Shi Liyang, Dai Jianwu
College of Biology, Hunan University, Changsha 410000, China.
State Key Laboratory of Molecular, Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
Regen Biomater. 2022 Dec 5;10:rbac097. doi: 10.1093/rb/rbac097. eCollection 2023.
Transplantation of adult spinal cord tissue (aSCT) is a promising treatment for spinal cord injury (SCI) basing on various types of neural cells and matrix components inside aSCT. However, long-term systemic administration of immunosuppressors (e.g. tacrolimus, TAC) is required for the survival of allogeneic tissue, which often associated with severe side effects such as infection, liver damageand renal failure. In this study, a triglycerol monostearate (TGM)-based TAC delivery system (e.g. TAC@TGM) with high drug loading concentration was developed, which possessed injectable properties as well as sustainable and immune-responsive drug release behaviors. In complete transected SCI model, locally injected TAC@TGM could reduce the infiltration of inflammation cells, enhance the survival of transplanted aSCT (e.g. Tuj-1 and NF neurons) and promote the recovery of locomotor function. Moreover, controlled release of TAC by TAC@TGM attenuated side effects of TAC on liver and kidneys compared with traditional systemic administration. More importantly, the developed TAC@TGM system provided a facile single dose of long-term immunosuppressive effect not just for aSCT transplantation, but also for other tissue/organ and cell transplantations.
基于成年脊髓组织（aSCT）内的各种神经细胞和基质成分，移植成年脊髓组织是治疗脊髓损伤（SCI）的一种很有前景的方法。然而，异体组织的存活需要长期全身给予免疫抑制剂（如他克莫司，TAC），这通常会伴有严重的副作用，如感染、肝损伤和肾衰竭。在本研究中，开发了一种基于单硬脂酸甘油酯（TGM）的TAC递送系统（如TAC@TGM），其具有高载药浓度，具备可注射性以及可持续和免疫响应性药物释放行为。在完全横断脊髓损伤模型中，局部注射TAC@TGM可减少炎症细胞浸润，提高移植aSCT（如Tuj-1和NF神经元）的存活率，并促进运动功能恢复。此外，与传统全身给药相比，TAC@TGM对TAC的控释减轻了TAC对肝脏和肾脏的副作用。更重要的是，所开发的TAC@TGM系统不仅为aSCT移植，也为其他组织/器官和细胞移植提供了一种简便的单剂量长期免疫抑制作用。
