血管化类器官的构建策略  

Construction strategy for vascularization of organoids

作　　者：刘明昱 范文娟[2] Liu Mingyu;Fan Wenjuan(Hainan Medical University,Haikou 571199,Hainan Province,China;Louhe Medical College,Luohe 462002,Henan Province,China)

机构地区：[1]海南医学院,海南省海口市571199 [2]漯河医学高等专科学校,河南省漯河市462002

出　　处：《中国组织工程研究》2025年第13期2774-2783,共10页Chinese Journal of Tissue Engineering Research

基　　金：河南省自然科学基金(222300420246),项目负责人:范文娟;漯河医专博士后科研项目(PR20210001),项目负责人:范文娟。

摘　　要：背景:有效促进类器官内部血管发生是目前类器官培养中的焦点问题,作为一种新近发展的生物培养技术,血管化的类器官在研究活体组织的发育、疾病形成的机制、组织替代疗法以及药物筛选等方面,都有很大的研究和应用价值。目的:对近年来类器官血管化的方法或策略进行归纳总结,分析类器官血管化形成机制以及构建策略,以期为更加深入地研究类器官的发生机制和为临床转化提供可靠的思路。方法:检索PubMed及中国知网数据库收录的相关文献。英文检索词为“organoids,Vascularization,Vascular,Vascular development,vessel”,中文检索词为“血管发生,血管生成,类器官,干细胞,血管化,预血管化”,最终纳入77篇文献进行归纳总结。结果与结论:①类器官血管化形成机制涉及3个关键因素,即种子细胞、细胞因子与细胞外基质。种子细胞为血管化类器官提供了关键的细胞来源,细胞因子为类器官内部的血管发生起了重要的信号引导作用,细胞外基质为血管细胞提供了外在的生长环境,促进类器官血管化的发生。②血管化类器官的构建策略包括细胞自我重组、微血管碎片渗入、宿主体内移植以及微流控芯片等。体外诱导多能干细胞向血管内皮祖细胞分化能顺利与邻近组织整合并具有血管生成的潜力,故可利用多能干细胞的自我重组功能构建血管化类器官。微血管碎片保留了其细胞复杂性、天然结构和表型可塑性,更利于模拟天然微血管从而促进类器官的血管化。宿主体内移植是目前类器官实现完整血液灌流的最佳方法,而微流控芯片则为实现类器官体外血液供应提供了解决方案。③类器官的多种构建策略如多类干细胞共分化、信号分子的精准调控、微血管渗入和活体宿主移植等,一定程度上在类器官中引入血管成分,使得类器官在功能和成熟度上更接近相应组织。�BACKGROUND:The effective promotion of internal angiogenesis in organoids is a current focal issue in organoid culture.Vascularized organoids,as a newly developed bioculture technology,have significant research and application value in the study of living tissue development,disease formation mechanisms,tissue replacement therapy,and drug screening.OBJECTIVE:To summarize the methods or strategies for vascularization of organoids in recent years,analyze the formation mechanism of vascularization of organoids and the construction strategies,with a view to providing reliable ideas for more in-depth study of the mechanism of organoid genesis and for clinical translation.METHODS:The authors utilized the PubMed and CNKI databases for related formation collection.The keywords were“organoids,vascularization,vascular,vascular development,vessel”in Chinese and English.Finally,77 papers were included for summarization.RESULTS AND CONCLUSION:(1)The mechanism of vascularization formation in organoid organs involves three key factors,namely seed cells,cytokines,and extracellular matrix.Seed cells provide the essential cell source for vascularized organoids;cytokines play an important role in guiding angiogenesis within organoids,and the extracellular matrix provides an external growth environment for vascular cells,promoting the occurrence of vascularized organoids.(2)The construction strategies of vascularized organoids include cell self-reorganization,microvascular fragment infiltration,transplantation into host,and microfluidic chip.In vitro induction of pluripotent stem cells to differentiate into endothelial progenitor cells can integrate with adjacent tissues and have the potential for angiogenesis,so pluripotent stem cells can be used to construct vascularized organoids by self-reorganization.Microvascular fragments retain their cellular complexity,natural structure,and phenotypic plasticity,which is more conducive to simulating natural microvessels and promoting vascularization of organoids.Transplantation into host

关 键 词：类器官 血管化 血管发生 自我重组 共培养 种子细胞 体内移植 内皮细胞 干细胞 综述 

分 类 号：R459.9[医药卫生—治疗学] R363[医药卫生—临床医学] Q189[生物学—神经生物学]