Luo Liwen, Gong Junfeng, Wang Zhouguang, Liu Yao, Cao Jiaming, Qin Jinghao, Zuo Rui, Zhang Hongyu, Wang Shuai, Zhao Ping, Yang Di, Zhang Mengjie, Wang Yanqiu, Zhang Junfeng, Zhou Yue, Li Changqing, Ni Bing, Tian Zhiqiang, Liu MingHan
Department of Orthopaedics, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
Institute of Immunology, PLA, Army Medical University (Third Military Medical University), Chongqing, China.
Bioact Mater. 2021 Dec 21;15:29-43. doi: 10.1016/j.bioactmat.2021.12.007. eCollection 2022 Sep.
Low back pain, mainly caused by intervertebral disc degeneration (IVDD), is a common health problem; however, current surgical treatments are less than satisfactory. Thus, it is essential to develop novel non-invasive surgical methods for IVDD treatment. Here, we describe a therapeutic strategy to inhibit IVDD by injecting hydrogels modified with the extracellular matrix of costal cartilage (ECM-Gels) that are loaded with cartilage endplate stem cells (CESCs). After loaded with CESCs overexpressing Sphk2 (Lenti-Sphk2-CESCs) and injected near the cartilage endplate (CEP) of rats in vivo, ECM-Gels produced Sphk2-engineered exosomes (Lenti-Sphk2-Exos). These exosomes penetrated the annulus fibrosus (AF) and transported Sphk2 into the nucleus pulposus cells (NPCs). Sphk2 activated the phosphatidylinositol 3-kinase (PI3K)/p-AKT pathway as well as the intracellular autophagy of NPCs, ultimately ameliorating IVDD. This study provides a novel and efficient non-invasive combinational strategy for IVDD treatment using injectable ECM-Gels loaded with CESCs that express Sphk2 with sustained release of functional exosomes.
下腰痛主要由椎间盘退变（IVDD）引起，是一个常见的健康问题；然而，目前的手术治疗效果并不理想。因此，开发用于IVDD治疗的新型非侵入性手术方法至关重要。在此，我们描述了一种治疗策略，即通过注射用肋软骨细胞外基质修饰的水凝胶（ECM-Gels）来抑制IVDD，该水凝胶负载有软骨终板干细胞（CESCs）。在体内将过表达Sphk2的CESCs（慢病毒-Sphk2-CESCs）负载到ECM-Gels中，并注射到大鼠软骨终板（CEP）附近后，ECM-Gels产生了Sphk2工程化外泌体（慢病毒-Sphk2-Exos）。这些外泌体穿透纤维环（AF）并将Sphk2转运至髓核细胞（NPCs）。Sphk2激活磷脂酰肌醇3激酶（PI3K）/p-AKT信号通路以及NPCs的细胞内自噬，最终改善IVDD。本研究提供了一种新型且高效的非侵入性联合策略，用于使用负载表达Sphk2的CESCs并持续释放功能性外泌体的可注射ECM-Gels治疗IVDD。
