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 surgic...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.展开更多
基金supported by the National Natural Science Foundation of China(Grant Number:81874028,81702182)the Research Program of Foundation Science and Application Technology of Chongqing(Grant Number:cstc2018jcyjAX0598)Basic Medical College Foundation of Army Medical University(2019JCZX10).
文摘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.
