牙髓再生组织工程中的细胞共培养体系

Cell co-culture system of dental pulp regenerative tissue engineering

背景:常规根管治疗去除所有牙髓组织会导致牙的生理功能和组织再生能力丧失,体外培养牙髓干细胞并使之形成牙髓样组织,再移植入髓腔内成为了理想的牙髓再生治疗方法。目的:汇总阐述通过共培养体系诱导牙髓干细胞形成牙髓样组织的研究进展,为牙髓组织再生的干细胞治疗方法提供思路。方法:第一作者于PubMed、中国知网和万方数据库检索时限为2022年5月以前发表的相关文献。英文检索词为“dental pulp regeneration,dental pulp stem cell,co-culture,tissue engineering,signaling pathway”,中文检索词为“牙髓再生、牙髓干细胞、共培养、组织工程、支架、信号通路”,纳入67篇符合标准的文献进行总结阐述。结果与结论:①共培养体系由细胞主体和组合细胞通过不同的组合方式构成。②现阶段共培养体系组合方式可分为直接共培养与间接共培养2种,生物支架材料的介入、培养条件的改变等作用又可将共培养结局分为二维和三维再生组织。③直接共培养通过细胞间接触构建生理性的细胞外基质以及利于干细胞增殖分化的微环境。④间接共培养解决了组合细胞来源不足、不同个体间免疫排异反应等问题,组合细胞产生的生物因子更易制成临床使用的药物和生物支架材料。⑤目前共培养体系在成血管有优越表现,但其他结构相关报道较少,且共培养结局形成的再生组织仍具有不确定性。同时,由于牙体解剖结构、排异反应等限制因素,将共培养体系生成的再生组织运用于临床仍然困难。

BACKGROUND:By removing all pulp tissue from the tooth,conventional root canal therapy will cause teeth to lose their physiological function and ability to regenerate tissue.The cultivation of dental pulp stem cells in vitro,the formation of dental pulp-like tissue,and the transplantation of this tissue into the pulp cavity have become an ideal method of dental pulp regeneration.OBJECTIVE:To summarize research progress on forming dental pulp-like tissue from dental pulp stem cells via a co-culture system,as well as provide ideas for stem cell therapy for dental pulp tissue regeneration.METHODS:The first author searched PubMed,CNKI,and Wanfang databases for relevant literature published before May 2022.The English search terms were“dental pulp regeneration,dental pulp stem cell,co-culture,tissue engineering,signaling pathway”,and the Chinese search terms were“dental pulp regeneration,dental pulp stem cells,co-culture,tissue engineering,scaffold,signaling pathway”.Totally 67 articles meeting the criteria were summarized and described.RESULTS AND CONCLUSION:(1)Different combinations of cells are used in co-culture systems to form the main body of the cell and the combined body.(2)Direct co-culture and indirect co-culture are the two types of combination modes at present.Through the intervention of biological scaffold materials and a change in culture conditions,the co-culture outcome can be divided into two-dimensional regenerated tissues and three-dimensional regenerated tissues.(3)Direct co-culture creates an extracellular matrix and microenvironment that facilitates stem cell proliferation and differentiation through intercellular contact.(4)Indirect co-culture addresses the problem of insufficient sources of combined cells and immune rejection between individuals.The biological factors produced by the combined cells can be more easily made into clinical drugs and biological scaffold materials.(5)Though the co-culture system has superior performance in angiogenesis,there are few reports on other structures,and the regeneration of tissue from the co-culture outcome is uncertain.Furthermore,there are limitations to applying newly generated tissue generated by the co-culture system to clinical practice due to tooth anatomical constraints and rejection mechanisms.