Dental follicle stem cells rescue the regenerative capacity of inflamed rat dental pulp through a paracrine pathway
Dental follicle stem cells rescue the regenerative capacity of inflamed rat dental pulp through a paracrine pathway
复制标题
牙囊干细胞通过旁分泌途径拯救发炎的大鼠牙髓的再生能力
DOI：
10.1186/s13287-020-01841-1
复制
发表时间：
2020-08-03
影响因子：
7.5
通讯作者：
Wei, Xi
中科院分区：
文献类型：
--
作者：
Hong, Hong;Chen, Xiaochuan;Wei, Xi
背景牙髓炎是一种常见的口腔疾病，以持续性炎症和牙髓自身修复受损为特征。基于间充质干细胞的微创活髓治疗（MSC-miVPT）是一种潜在的治疗方法，但由于获取间充质干细胞的困难，其应用受到限制。最近，我们揭示了大鼠牙囊干细胞（rDFSCs）对急性肺损伤的免疫调节作用。本研究的重点是旁分泌作用的rDFSCs对大鼠损伤牙髓的炎症和再生，以检测DFSCs是否是一个潜在的候选人MSC-miVPT. MethodsConditionedmedium从rDFSCs（rDFSC-CM）施加到脂多糖（LPS）诱导的炎症大鼠牙髓细胞（rDPC）。采用RT-qPCR、Western blotting、免疫荧光、CCK-8法、流式细胞术、创伤愈合试验和Masson染色等方法检测rDPC的炎症和再生情况。结果rDFSC-CM下调ERK 1/2和NF-κB信号通路，抑制IL-1β、IL-6和TNF-α的表达，促进IL-4和TGF-β的表达，从而减轻rDPC炎症反应。rDFSC-CM增强炎性rDPC的体外增殖、迁移和牙源性分化及其体内异位牙本质形成。此外，rDFSC-CM还可以抑制大鼠牙髓炎中炎症细胞的浸润，并触发损伤部位周围部分成牙本质细胞样细胞Runx 2的表达，这些作用有利于炎症牙髓的修复。结论rDFSC-CM具有治疗潜力，可以通过免疫调节机制拯救炎症大鼠牙髓的再生。显示了DFSCs在生物再生牙髓学中的应用前景。
BackgroundPulpitis is a common dental disease characterized by sustained inflammation and impaired pulp self-repair. Mesenchymal stem cell-based minimally invasive vital pulp therapy (MSC-miVPT) is a potential treatment method, but its application is limited by the difficulty in acquiring MSCs. We recently revealed the immunomodulatory effects of rat dental follicle stem cells (rDFSCs) on acute lung injury. The present study focused on the paracrine effects of rDFSCs on the inflammation and regeneration of rat injured dental pulp to detect whether DFSCs are a potential candidate for MSC-miVPT.MethodsConditioned medium from rDFSCs (rDFSC-CM) was applied to lipopolysaccharide (LPS)-induced inflammatory rat dental pulp cells (rDPCs). The inflammation and regeneration of rDPCs were detected by RT-qPCR, Western blotting, immunofluorescence staining, Cell Counting Kit-8 (CCK-8) assay, flow cytometry, wound-healing assay, and Masson’s staining. The effects of rDFSC-CM on inflamed rat dental pulp were further evaluated by hematoxylin-eosin and immunohistochemical staining.ResultsrDFSC-CM downregulated the ERK1/2 and NF-κB signaling pathways, which resulted in suppression of the expression of IL-1β, IL-6, and TNF-α and promotion of the expression of IL-4 and TGF-β, and these findings lead to the attenuation of rDPC inflammation. rDFSC-CM enhanced the in vitro proliferation, migration, and odontogenic differentiation of inflammatory rDPCs and their in vivo ectopic dentinogenesis. Furthermore, rDFSC-CM inhibited inflammatory cell infiltration in rat pulpitis and triggered Runx2 expression in some of the odontoblast-like cells surrounding the injured site, and these effects were conducive to the repair of inflamed dental pulp.ConclusionsrDFSC-CM exhibits therapeutic potential by rescuing the regeneration of the inflamed rat dental pulp through an immunomodulatory mechanism, indicating the application prospects of DFSCs in biological regenerative endodontics.