Dental pulp stem cell-derived apoptotic bodies regulate macrophage polarization and inflammatory response

口腔疾病防治

GONG Shengkai¹  DOU Geng²  LI Zihan²  LIU Siying²  YANG Xiaoshan²  WANG Wei³  LIU Shiyu³ 

[1]1. School of Basic Medicine, the Fourth Military Medical University2.

[2]State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, the Fourth Military Medical University

[3]State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Department of Operative Dentistry and Endodontics, School of Stomatology, the Fourth Military Medical University

关键词: dental pulp stem cells;    macrophages;    macrophages polarization;    inflammatory response;    apoptosis;    apoptotic bodies;    tissue regeneration;    stem cell transplantation;    inflammatory regulation;   

DOI  :  10.12016/j.issn.2096-1456.2022.01.003

来源: DOAJ

【 摘 要 】

Objective To investigate the effects of apoptotic bodies (ABs) derived from dental pulp stem cells (DPSCs) on macrophage polarization and inflammation response in vivo. Methods Human DPSCs were extracted, cultured and identified. Staurosporine was used to apoptosis induction and differential methods were performed for ABs identification. The in vitro cultured macrophages were divided into 3 groups: solvent control, lipopolysaccharide (LPS), and the LPS+ABs. The macrophages were stimulated with LPS to induce inflammation followed by ABs treatment. In the untreated group, macrophages were added with an equal amount of solvent. The specific uptake of ABs by macrophages, the expression level of CD206 and the levels of inflammatory cytokines were analyzed. The mouse models of cutaneous wounds and dextran sulfate sodium (DSS)-induced colitis were established, and the mice were randomly divided into 3 groups: the PBS-treated group, the DPSCs-treated group, and the ABs-treated group. The mice were injected with the same volume of PBS, DPSCs and ABs, respectively. The body weight, histological pathology, the expression levels of CD206 and cytokines, and the extent of tissue regeneration were measured. Results DPSCs and ABs derived from DPSCs were successfully isolated and characterized. ABs could be taken up by macrophage. While lipopolysaccharide(LPS) induced production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), ABs significantly reduced the levels of these pro-inflammatory cytokines and increased the expression of transforming growth factor-β (TGF-β) and CD206 (P < 0.01). In the cutaneous inflammatory wound model, the wound closure rate in mice intravenously injected with ABs was significantly accelerated (P < 0.05). The administration of ABs markedly reduced the pro-inflammatory factors levels and increased the CD206+ cell number. In the colitis model, treatment with ABs markedly reduced the loss in bodyweight (P < 0.05), recovered the colon length (P < 0.01), and significantly increased the CD206+ cell number. Conclusion DPSCs-derived ABs could enhance macrophage M2 polarization and attenuate inflammation. Therefore, ABs could be used as a promising cell replacement for inflammatory regulation and tissue regeneration.

【 授权许可】

Unknown