细胞衍生物在牙周组织再生中的应用

Application of cell derivative in periodontal regeneration

背景:包括脱细胞外基质、外泌体、凋亡囊泡及条件培养基在内的细胞衍生物具有免疫调节、促进血管形成、骨再生、韧带重塑的作用,具有促进干细胞的趋化、迁移、增殖和黏附的能力,其优良的特性使其在牙周组织工程方面有良好的应用前景和临床转化价值。目的:综述细胞外基质、外泌体、凋亡囊泡和条件培养基4种细胞衍生物的特点及在牙周复杂组织结构再生修复领域的作用及最新进展。方法:以“regeneration,periodontal tissue,tissue engineering,decellularized matrix,exosome,apoptotic extracellular vesicle,condition medium”为英文检索词,以“再生、牙周组织、组织工程、外泌体、凋亡囊泡、细胞外基质、条件培养基”为中文检索词,检索PubMed和中国知网数据库发表的相关文献,最后纳入76篇文献进行分析与讨论。结果与结论:①在4种细胞衍生物中,细胞外基质具备最好的机械性能和纤维结构,在牙周组织工程中作为生物支架提供物理化学信号并参与力学信号转导,适用于需要支架支持的牙周再生场景;近年来,可溶性脱细胞基质生物墨水的发展为个性化牙周缺损再生支架的制作提供了可能。②外泌体是成分最单一的细胞衍生物,具备免疫调节的作用,促进细胞迁移分化;作为载体,可用于搭载目标分子调控牙周再生,促进韧带重塑和骨再生,适合用于牙周组织工程载药的场景。③凋亡囊泡是凋亡过程中产生的、具有强免疫调节作用的胞外囊泡,可以招募干细胞和巨噬细胞,并通过信号转导决定干细胞的命运,可以用于需要改善免疫调节的场合以促进牙周再生,工程化胞外囊泡是目前研究的热点,有望用于靶向调节体内免疫。④条件培养基的提取简单,且是完全无创的,它为组织再生提供必需的营养物质和生长因子,这些成分对于成功的牙周再生至关重要,因此条件培养基尤其适用于体外研究细胞之间相互作用,在未来的高通量检测中具有举足轻重的地位。

BACKGROUND:Cell derivative is cell-derived bioactive components,including decellularized extracellular matrix,exosome,apoptotic extracellular vesicle,and conditioned medium,has the effects on immune regulation,promoting angiogenesis,bone regeneration,ligament remodeling,and is capable of promoting stem cell chemotherapy,migration,proliferation,and adhesion.Its excellent characteristics make it a promising biomaterial for application and clinical translation in the field of periodontal tissue engineering.OBJECTIVE:To review the characteristics of cell derivatives(decellularized extracellular matrix,exosome,apoptotic extracellular vesicle,and conditioned medium)and its effect and the latest progress in the field of regenerative restoration of periodontal complex tissue structures.METHODS:We searched the articles on CNKI and PubMed databases with the search terms“regeneration,periodontal tissue,tissue engineering,decellularized matrix,exosome,apoptotic extracellular vesicle,condition medium”in Chinese and English,respectively.Finally,76 articles were included for analysis and discussion.RESULTS AND CONCLUSION:(1)Among those four cell derivatives,the decellularized extracellular matrix has the best mechanical properties and fibrous structure,serving as a biomimetic scaffold to provide physiochemical signals and participate in mechanical signaling in periodontal tissue engineering,providing supporting effect suitable for periodontal regeneration.Recently,the development of soluble decellularized extracellular matrix bioinks has enabled the fabrication of regenerative scaffolds for personalized periodontal defects.(2)Exosomes are the simplest cell derivatives that have immunomodulatory capacity,promoting cell migration and differentiation.As a carrier,they can be used to carry target molecules to regulate periodontal regeneration,promote ligament remodeling and bone regeneration,and are suitable for periodontal tissue engineering.(3)Apoptotic vesicles generated from apoptotic cells have a strong immunomodulatory effect and can recruit stem cells and macrophages,which determine the fate of stem cells through signal transduction and can enhance immunomodulation to promote periodontal regeneration.Engineered extracellular vesicle is considered to have the potential to initiate targeted internal immunomodulation.(4)The extraction of conditioned medium is simple and completely noninvasive,which provides essential nutrients and growth factors for tissue regeneration.These components are crucial for successful periodontal regeneration.Therefore,the conditioned medium is especially suitable for studying the interactions between cells in vitro and has an important role in high-throughput detection in the future.