Mesenchymal stem cell-derived exosomes: Toward cell-free therapeutic strategies in regenerative medicine

Mesenchymal stem cells(MSCs)are multipotent stem cells with marked potential for regenerative medicine because of their strong immunosuppressive and regenerative abilities.The therapeutic effects of MSCs are based in part on their secretion of biologically active factors in extracellular vesicles known as exosomes.Exosomes have a diameter of 30-100 nm and mediate intercellular communication and material exchange.MSC-derived exosomes(MSC-Exos)have potential for cell-free therapy for diseases of,for instance,the kidney,liver,heart,nervous system,and musculoskeletal system.Hence,MSC-Exos are an alternative to MSCbased therapy for regenerative medicine.We review MSC-Exos and their therapeutic potential for a variety of diseases and injuries.

Use of priming strategies to advance the clinical application of mesenchymal stromal/stem cell-based therapy

Mesenchymal stromal/stem cells(MSCs)have garnered significant attention in the field of regenerative medicine due to their remarkable therapeutic potential.MSCs play a pivotal role in maintaining tissue homeostasis and possess diverse functions in tissue repair and recovery in various organs.These cells are charac-terized by easy accessibility,few ethical concerns,and adaptability to in vitro cultures,making them a valuable resource for cell therapy in several clinical conditions.Over the years,it has been shown that the true therapeutic power of MSCs lies not in cell engraftment and replacement but in their ability to produce critical paracrine factors,including cytokines,growth factors,and exosomes(EXOs),which modulate the tissue microenvironment and facilitate repair and regeneration processes.Consequently,MSC-derived products,such as condi-tioned media and EXOs,are now being extensively evaluated for their potential medical applications,offering advantages over the long-term use of whole MSCs.However,the efficacy of MSC-based treatments varies in clinical trials due to both intrinsic differences resulting from the choice of diverse cell sources and non-standardized production methods.To address these concerns and to enhance MSC therapeutic potential,researchers have explored many priming strategies,including exposure to inflammatory molecules,hypoxic conditions,and three-dimensional culture techniques.These approaches have optimized MSC secretion of functional factors,empowering them with enhanced immunomodulatory,angiogenic,and regenerative properties tailored to specific medical conditions.In fact,various priming strategies show promise in the treatment of numerous diseases,from immune-related disorders to acute injuries and cancer.Currently,in order to exploit the full therapeutic potential of MSC therapy,the most important challenge is to optimize the modulation of MSCs to obtain adapted cell therapy for specific clinical disorders.In other words,to unlock the complete potential of MSCs in regenerative medicine,it is crucial to identify the most suitable tissue source and develop in vitro manipulation protocols specific to the type of disease being treated.

牙髓血运重建术治疗年轻恒牙外伤继发性牙髓坏死疗效观察

目的:探究牙髓血运重建术与根管治疗术治疗年轻恒牙外伤后继发性牙髓坏死的疗效。方法:选择2018年7月-2019年7月诊断为年轻恒牙外伤后继发性牙髓坏死的患者106例,随机分为观察组和对照组,观察组(53例)实施牙髓血运重建术(Regenerative endodontic procedures,REPs),对照组(53例)实施传统根管治疗术。并在治疗24个月后随访治疗效果,根据临床症状和X线片进行评价,分析两组患者治疗后的治愈率。结果:治疗后,观察组总有效率(96.23%)显著高于对照组(75.47%)(P<0.05);治疗后,两组患者的牙冠根比、牙根管壁厚度均明显增加(P<0.05),观察组治疗后牙冠根比、牙根管壁厚度显著高于对照组(P<0.05);治疗后患者的咬合力也显著增强,咬合时间显著降低(P<0.05),观察组治疗后咬合能力显著优于对照组(P<0.05)。结论:REPs治疗年轻恒牙外伤后继发性牙髓坏死的疗效显著优于常规根管治疗,且增强了牙根的坚固和稳定程度,具有较高的安全性。

再生性牙髓治疗的研究进展

牙髓作为牙体结构中唯一的软组织结构,具有感觉、营养等诸多功能,但牙髓本身却极易受到外界因素影响而坏死。目前针对牙髓坏死最常用的治疗办法是根管治疗术,但根管治疗后的牙齿容易发生二次感染,出现牙根纵裂等不良预后。再生性牙髓治疗旨在替换受损牙齿结构的生物程序,包括牙本质、牙根结构以及牙髓-牙本质复合体的细胞,展现出了解决临床症状、实现牙根甚至牙髓再生等巨大优势。在牙髓干细胞被发现后,再生性牙髓治疗又展现出了新的活力,细胞移植、细胞归巢等治疗方案发展迅速并展现出广阔的应用前景。

基于炎症微环境调控组织工程再生性牙髓治疗

背景:近年来,再生性牙髓治疗概念随着组织工程的发展逐渐形成,炎症微环境在调控牙髓再生方面起着关键作用。目的:文章从炎症牙髓微环境变化出发,着眼于炎症与再生平衡,重点介绍炎症微环境中组织工程再生性牙髓治疗的研究进展,为未来再生性牙髓治疗的研究提供参考。方法:在PubMed和中国知网数据库中进行检索,中文检索词为“牙髓再生,炎症,再生性牙髓治疗,组织工程”;英文检索词为“pulp regeneration,inflammation,regenerative endodontic therapy,tissue engineering”,分别检索2013-2023年发表的相关文献,最终纳入61篇文献进行综述分析。结果与结论:①牙髓炎症微环境的变化涉及一系列细胞与分子反应,随炎症进展,微环境对组织修复的作用弊大于利。②炎症通过干细胞募集及激活补体系统等方式促进牙髓再生,也能通过免疫抑制、纤维化破坏再生过程。③组织工程三要素(干细胞、生长因子及支架材料)协同介导炎症反应以恢复炎症-再生平衡,如利用白细胞介素6调节牙髓干细胞功能介导炎症微环境以促进牙髓再生。④当前研究缺乏对感染、炎症问题的关注,牙髓炎症微环境的变化机制尚不清晰,通过有机结合组织工程再生性牙髓治疗的三要素调控炎症微环境,构建再生微环境,精准地调控炎症-再生平衡或是提高临床适用性的突破口之一,但该部分研究仍存在较大空缺,期望未来的研究就如何实现炎症环境下的牙髓再生展开更多的探索,也还需更多动物实验、随机临床试验为组织工程再生性牙髓治疗的临床实践奠定基础。

无细胞再生性牙髓治疗的现状及展望

患牙髓/根尖周病变的牙齿经过根管治疗后可得以保留,但是失去牙髓的患牙易发生再次感染和牙纵裂等并发症。随着组织工程和生物材料的发展,以生物学为基础的牙髓牙本质复合体再生或修复治疗成为可能。无细胞再生性牙髓治疗已经成为儿童和青少年年轻恒牙牙髓坏死的有效治疗方法,对成熟恒牙的治疗也在探索中。

影响年轻恒牙牙髓再生术预后的常见因素

牙髓再生术目前在年轻恒牙的牙髓坏死和根尖周炎治疗中有着广泛的应用,总体成功率较高。但是,随着病例观察时间的延长,越来越多的失败病例逐渐出现。牙髓再生术是一项技术敏感性较高的治疗方法,该文旨在对牙髓再生术预后产生影响的潜在因素进行综述,为操作者在以后的治疗中规避不良因素提供建议。

The secretome of endothelial progenitor cells: a potential therapeutic strategy for ischemic stroke

Ischemic stroke continues to be a leading cause of mortality and morbidity in the world. Despite recent advances in the field of stroke medicine, thrombolysis with recombinant tissue plasminogen activator remains as the only pharmacological therapy for stroke patients. However, due to short therapeutic window(4.5 hours of stroke onset) and increased risk of hemorrhage beyond this point, each year globally less than 1% of stroke patients receive this therapy which necessitate the discovery of safe and efficacious therapeutics that can be used beyond the acute phase of stroke. Accumulating evidence indicates that endothelial progenitor cells(EPCs), equipped with an inherent capacity to migrate, proliferate and differentiate, may be one such therapeutics. However, the limited availability of EPCs in peripheral blood and early senescence of few isolated cells in culture conditions adversely affect their application as effective therapeutics. Given that much of the EPC-mediated reparative effects on neurovasculature is realized by a wide range of biologically active substances released by these cells, it is possible that EPC-secretome may serve as an important therapeutic after an ischemic stroke. In light of this assumption, this review paper firstly discusses the main constituents of EPC-secretome that may exert the beneficial effects of EPCs on neurovasculature, and then reviews the currently scant literature that focuses on its therapeutic capacity.

Mesenchymal stem cell-derived exosome:The likely game-changer in stem cell research

Stem cell research is a promising area of transplantation and regenerative medicine with tremendous potential for improving the clinical treatment and diagnostic options across a variety of conditions and enhancing understanding of human development.Over the past few decades,mesenchymal stem cell(MSCs)studies have exponentially increased with a promising outcome.However,regardless of the huge investment and the research attention given to stem cell research,FDA approval for clinical use is still lacking.Amid the challenges confronting stem cell research as a cellbased product,there appears to be evidence of superior effect and heightened potential success in its expressed vesicles,exosomes,as cell-free products.In addition to their highly desirable intrinsic biologically unique structural,compositional,and morphological characteristics,as well as predominant physiochemical stability and biocompatibility properties,exosomes can also be altered to enhance their therapeutic capability or diagnostic imaging potential via physical,chemical,and biological modification approaches.More importantly,the powerful therapeutic potential and superior biological functions of exosomes,particularly,regarding engineered exosomes as cell-free products,and their utilization in a new generation of nanomedicine treatment,vaccination,and diagnosis platforms,brings hope of a change in the near future.This viewpoint discusses the trend of stem cell research and why stem cell-derived exosomes could be the game-changer.

再生性牙髓治疗的生物学基础及临床探索

再生性牙髓治疗是基于组织工程学的一种治疗手段,目标是实现牙髓-牙本质复合体再生,促使牙髓坏死年轻恒牙的牙根继续发育。方法上与其他组织工程学治疗技术一样依赖种子细胞、支架材料和生长因子这3个要素。该技术提出至今20年来,文献中名称多样,内涵各有异同。本文就再生性牙髓治疗的名称演变、生物学基础、临床考量以及未来科学研究方向进行梳理、分析和阐述,以明了尚未解决的科学问题,引导再生性牙髓治疗在临床上合理开展与规范操作。

表没食子儿茶素没食子酸酯对人牙髓干细胞增殖和迁移影响的初步研究

目的:体外探讨表没食子儿茶素没食子酸酯(epigallocatechin gallate,EGCG)对人牙髓干细胞(dental pulp stem cells,DPSCs)增殖和迁移的影响。方法:从人牙髓组织分离培养DPSCs,并通过形态学、三向分化实验及流式细胞术进行鉴定。通过CCK-8、Transwell实验和划痕实验检测EGCG对DPSCs体外增殖和迁移的影响。结果:分离培养的DPSCs呈长梭形,贴壁生长,具备三向分化潜能,且CD73、CD90和CD105阳性表达,CD34阴性表达,表明分离获得的DPSCs为间充质干细胞。2.5~20μmol/L的EGCG具有促进DPSCs增殖的作用,且在5μmol/L时显著增强细胞迁移。结论:低浓度EGCG可促进DPSCs的增殖和迁移能力,为EGCG在基于细胞归巢的牙髓-牙本质复合体再生领域的应用提供参考。

浓缩生长因子用于年轻恒牙根尖周炎再生性牙髓治疗2例及文献复习

浓缩生长因子(CGF)是一种血小板浓缩物,是利用血液样本和特殊的离心设备制备而成的含有高浓度生长因子的纤维蛋白团块,具有较好的可塑性和促再生能力。其中,生长因子可作为良好的支架基质,能够将未分化的间充质细胞吸引到相应部位,促进血管生成和细胞增殖;而纤维蛋白形成的三维网状结构,则使得生长因子、白细胞和成纤维细胞等更易附着于蛋白表面,为细胞的增殖分化提供基质,最终促进牙髓组织修复。