The promising potential of small extracellular vesicles in the field of intervertebral disc repair - A comprehensive meta-analysis

jingyao ye¹Liu Xuehong²Wen Xiaohui²kunyin li²yongge guan^2*

• ¹Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
• ²Guangzhou University of Chinese Medicine, Guangzhou, China

BACKGROUND CONTEXT: IDD is one of the main factors causing chronic LBP and disability, which seriously affects the quality of life of patients and brings heavy social and economic burden. At present, conservative treatment and surgical methods have limitations, which can not reverse the disease process. In recent years, sEVs as a new type of intercellular communication medium have attracted extensive attention. SEVs have low immunogenicity, good biocompatibility and stability, and can delay or reverse intervertebral disc degeneration by regulating the synthesis of extracellular matrix, inhibiting apoptosis and inflammatory reaction. Compared with cell therapy, SEVs not only retains the therapeutic effect, but also avoids the problems of immune rejection and microenvironment limitation, showing broad application prospects in the treatment of intervertebral disc degeneration. PURPOSE: This study systematically reviewed and analysed the progress of preclinical studies on the application of exosomes for the treatment of IDD to provide evidence for future studies. Study Design: This study is performed as a systematic review and meta-analysis. Methods: The following databases were extensively searched to identify relevant studies: PubMed, Embase, The Cochrane Library and Web of Science. Two trained researchers independently screened the literature, extracted data and assessed the quality of the literature. Further data processing of the collected studies was performed using Review Manager 5.4 and R version 4.1.1 software. Results: A total of 27 animal studies were analysed in this study and all included studies were randomised controlled trials. This study suggests that the best efficacy of transplantation therapy is achieved by selecting cell line-derived sEVs in the early stages of IDD, 4W may be the optimal treatment cycle for imaging improvement, and 8W may be the optimal treatment cycle at the cellular-molecular level. Conclusions: The present study demonstrated that cellular sEVs can effectively improve disc height index (DHI) and magnetic resonance(MR) grading as well as hematoxylin-eosin staining(HE) grading in a mouse model of IDD. Therefore sEVs have a promising future in preclinical studies for the treatment of IDD, especially for the improvement of myeloid cells, with potential for further research as well as clinical translation.