Injectable cartilage matrix hydrogel loaded with cartilage endplate stem cells engineered to release exosomes for non-invasive treatment of intervertebral disc degeneration
Liwen Luo, Junfeng Gong, Zhouguang Wang, Yao Liu, Jiaming Cao, Jinghao Qin, Rui Zuo, Hongyu Zhang, Shuai Wang, Ping Zhao, Di Yang, Mengjie Zhang, Yanqiu Wang, Junfeng Zhang, Yue Zhou, Changqing Li, Bing Ni, Zhiqiang Tian, Minghan Liu
Abstract
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.