Li Ziyue, Liang Yan, Pan Kuangwu, Li Hui, Yu Mei, Guo Weihua, Chen Guoqing, Tian Weidong
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Cell Prolif. 2017 Aug;50(4). doi: 10.1111/cpr.12353.
Schwann cells (SCs) are the principal glial cells in peripheral nerve system, involved in neuropathies with great regenerative potential. Dental pulp cells have been reported to maintain neurogenic potential. In contrast, the regulatory role of SCs on human dental pulp cells (hDPCs) development remains undefined.
SC secretion and SC-derived extracellular vesicles (EVs) were collected and used to treat hDPCs; and proliferation and multiple differentiation of hDPCs were detected after EVs treatments. Finally, we analysed the proteomes of SC-EVs and SCs through mass spectrum.
In this study, we found SC secretion showed a predominantly regulatory role on the development of hDPCs. Further, we identified EVs from SC secretion with similar function as SC secretion in regulating hDPCs proliferation and multipotency. And expression of transcription factor Oct4 was upregulated after treatment of both SC secretion and EVs, as well as Sox2 and Nanog. We detected abundant enrichment of Oct4 in EVs, which might be responsible for the upregulation of stem cell-related genes in hDPCs. Through proteome and western blot analysis, we found enriched TGFβs in EVs, indicating that accelerated hDPCs proliferation may be mediated by activated TGFβ-Samd and TGFβ-MAPK signalling.
In summary, our study sheds light on critical regulatory ability of SC-derived EVs on hDPCs proliferation and multipotency, suggesting great implications for seeding cells used in tissue engineering.
施万细胞(SCs)是周围神经系统中的主要神经胶质细胞,参与具有巨大再生潜力的神经病变。据报道,牙髓细胞具有维持神经源性潜力。相比之下,SCs对人牙髓细胞(hDPCs)发育的调节作用仍不明确。
收集SCs分泌产物和SCs衍生的细胞外囊泡(EVs),用于处理hDPCs;在EVs处理后检测hDPCs的增殖和多向分化。最后,我们通过质谱分析了SC-EVs和SCs的蛋白质组。
在本研究中,我们发现SCs分泌产物对hDPCs的发育显示出主要的调节作用。此外,我们从SCs分泌产物中鉴定出的EVs在调节hDPCs增殖和多能性方面具有与SCs分泌产物相似的功能。在SCs分泌产物和EVs处理后,转录因子Oct4以及Sox2和Nanog的表达均上调。我们检测到EVs中Oct4大量富集,这可能是hDPCs中干细胞相关基因上调的原因。通过蛋白质组和蛋白质印迹分析,我们发现EVs中TGFβs富集,表明hDPCs增殖加速可能由激活的TGFβ-Samd和TGFβ-MAPK信号介导。
总之,我们的研究揭示了SCs衍生的EVs对hDPCs增殖和多能性的关键调节能力,提示其对组织工程中种子细胞具有重要意义。