心肌补片:细胞来源、完善策略及最佳制作方法分析  

Myocardial patch:cell sources,improvement strategies,and optimal production methods

作　　者：胡威 邢健 陈广新[2] 陈泽娥 赵艺 乔丹 欧阳昆富 黄文华 Hu Wei;Xing Jian;Chen Guangxin;Chen Zee;Zhao Yi;Qiao Dan;Ouyang Kunfu;Huang Wenhua(School of Basic Medical Sciences,Fujian Medical University,Fuzhou 350122,Fujian Province,China;School of Medical Imaging,Mudanjiang Medical University,Mudanjiang 157011,Heilongjiang Province,China;Department of Cardiac Surgery,Peking University Shenzhen Hospital,Shenzhen 518036,Guangdong Province,China;School of Chemical Biology and Biotechnology,Shenzhen Graduate School,Peking University,Shenzhen 518055,Guangdong Province,China;Department of Academic Affairs,Harbin Institute of Technology(Shenzhen),Shenzhen 518055,Guangdong Province,China;Department of Pathology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310016,Zhejiang Province,China;State Key Discipline of Human Anatomy,Key Laboratory of Medical Biomechanics of Guangdong Province,Guangdong Medical 3D Printing Application Transformation Engineering Technology Research Center,School of Basic Medical Sciences,Southern Medical University,Guangzhou 510515,Guangdong Province,China;Shenzhen Pingshan People’s Hospital(Pingshan General Hospital of Southern Medical University),Shenzhen 518118,Guangdong Province,China;Third Affiliated Hospital of Southern Medical University,Guangdong Medical 3D Printing Application Transformation and Innovation Platform,Guangzhou 510000,Guangdong Province,China)

机构地区：[1]福建医科大学基础医学院,福建省福州市350122 [2]牡丹江医学院医学影像学院,黑龙江省牡丹江市157011 [3]北京大学深圳医院心外科,广东省深圳市518036 [4]北京大学深圳研究生院化学生物学与生物技术学院,广东省深圳市518055 [5]哈尔滨工业大学(深圳)教务部,广东省深圳市518055 [6]浙江大学医学院附属邵逸夫医院病理科,浙江省杭州市310016 [7]南方医科大学基础医学院人体解剖学国家重点学科,广东省医学生物力学重点实验室,广东省医学3D打印应用转化工程技术研究中心,广东省广州市510515 [8]深圳市坪山区人民医院(南方医科大学坪山总医院),广东省深圳市518118 [9]南方医科大学第三附属医院,广东省医学3D打印应用转化创新平台,广东省广州市510000

出　　处：《中国组织工程研究》2024年第17期2723-2730,共8页Chinese Journal of Tissue Engineering Research

基　　金：国家重点研发计划(2022YFB4600600),项目负责人:黄文华;国家自然科学基金(31972915,32271181),项目负责人:黄文华;国家自然科学基金面上项目(81970421,82170235),项目负责人:欧阳昆富;中国博士后科学基金(2021M702224,2022T150430),项目负责人:陈泽娥;广东省基础与应用基础研究基金(2020B1515120001),项目负责人:黄文华;广东省自然科学基金面上项目(2023A1515011842),项目负责人:欧阳昆富;广东省基础与应用基础研究基金项目(2019A1515111178),项目负责人:赵艺;牡丹江医学院科学基金火炬计划(2022-MYHJ-004),项目负责人:邢健;深圳市自然科学基金(JCYJ20190808174001746,JCYJ20210324105407019),项目负责人:欧阳昆富;深港脑科学创新研究院项目(2019SHIBS0004,2023SHIBS0004),项目负责人:欧阳昆富。

摘　　要：背景:心肌补片是一种修复损伤心肌的有效方式,但目前使用哪种细胞制作心肌补片和如何使心肌补片在体内发挥最大的治疗效果还存在争议。目的:通过综述心肌补片的细胞来源和完善心肌补片的策略来寻找出制作心肌补片的最佳方法。方法:由第一作者应用计算机以“cell sheet,cell patch,cardiomyocytes,cardia progenitor cells,fibroblasts,embryonic stem cell,mesenchymal stem cells”等为英文检索词检索PubMed和Web of Science数据库;以“心肌补片,生物3D打印,心肌”为中文检索词检索中国知网和万方数据库,经过入组筛选后,最终纳入94篇文献进入结果分析。结果与结论:①心肌补片的细胞来源主要分为3类:分别是体细胞、单能干细胞和多能干细胞。心肌补片的细胞来源丰富,但是并不是所有的细胞都适合制作心肌补片,例如,成纤维细胞和骨骼肌母细胞制成的心肌补片会有致心律失常的风险,间充质干细胞在体内的作用时间短并且存在伦理方面的问题。随着诱导式多功能干细胞的发现,为制作心肌补片提供了一个可靠的细胞来源。②心肌补片的制作方法有两种:一种是使用细胞片技术,另一种是使用生物3D打印技术。细胞片技术可完整保留细胞外基质成分,可以最大程度地模拟细胞在体内的生长循环,但是想要通过细胞片技术获得具有三维结构的心肌补片还存在困难。而生物3D打印技术可以通过计算机个性化设计获得具有三维结构的心肌补片。③完善心肌补片的策略主要包括:多种细胞共同培养后制作成心肌补片、改进生物3D打印技术中的墨水配方和支架成分、提高心肌补片的治疗效果、抑制移植后的免疫排斥反应和完善干细胞的分化培养方案。④目前还没有制作心肌补片的最佳细胞来源和制作方法,单靠某一种细胞或者某一种技术所获得的心肌补片常无法达到预期的治疗效果,因�BACKGROUND:Myocardial patches are used as an effective way to repair damaged myocardium,and there is controversy over which cells to use to make myocardial patches and how to maximize the therapeutic effect of myocardial patches in vivo.OBJECTIVE:To find out the best way to make myocardial patches by overviewing the cellular sources of myocardial patches and strategies for perfecting them.METHODS:The first author searched PubMed and Web of Science databases by using“cell sheet,cell patch,cardiomyocytes,cardiac progenitor cells,fibroblasts,embryonic stem cell,mesenchymal stem cells”as English search terms,and searched CNKI and Wanfang databases by using“myocardial patch,biological 3D printing,myocardial”as Chinese search terms.After enrollment screening,94 articles were ultimately included in the result analysis.RESULTS AND CONCLUSION:(1)The cellular sources of myocardial patches are mainly divided into three categories:somatic cells,monoenergetic stem cells,and pluripotent stem cells,respectively.There are rich sources of cells for myocardial patches,but not all of them are suitable for making myocardial patches,e.g.,myocardial patches made from fibroblasts and skeletal myoblasts carry a risk of arrhythmogenicity,and mesenchymal stem cells have a short in vivo duration of action and ethical concerns.With the discovery of induced multifunctional stem cells,a reliable source of cells for making myocardial patches is available.(2)There are two methods of making myocardial patches.One is using cell sheet technology.The other is using biological 3D printing technology.Cell sheet technology can preserve the extracellular matrix components intact and can maximally mimic the cell growth ring in vivo.However,it is still difficult to obtain myocardial patches with three-dimensional structure by cell sheet technology.Biologicasl 3D printing technology,however,can be used to obtain myocardial patches with three-dimensional structures through computerized personalized design.(3)The strategies for perfecting myocardial

关 键 词：心肌补片 多能干细胞 3D打印 生物墨水 细胞片 综述 间充质干细胞 免疫反应 心肌细胞 骨骼肌母细胞 

分 类 号：R459.9[医药卫生—治疗学] R363[医药卫生—临床医学] R605