透明质酸水凝胶包裹骨髓间充质干细胞改善大鼠心肌梗死后心功能  

Combination of hyaluronic acid and bone marrow mesenchymal stem cells promotes cardiac function after myocardial infarction

作　　者：商青青 周建业[1] 李凯[1] 孙嘉康[1] 孟健[1] 李君[1] Shang Qing-qing;Zhou Jian-ye;Li Kai;Sun Jia-kang;Meng Jian;Li Jun(State Key Laboratory of Cardiovascular Disease,Fuwai Hospital,National Center for Cardiovascular Diseases,Peking Union Medical College and Chinese Academy of Medical Sciences,Beijing 100037,China;Department of Pain,Affiliated Hospital of Binzhou Medical University,Binzhou 256603,Shandong Province,China)

机构地区：[1]中国医学科学院,北京协和医学院,国家心血管病中心,阜外心血管病医院,心血管疾病国家重点实验室,北京市100037 [2]滨州医学院附属医院疼痛科,山东省滨州市256603

出　　处：《中国组织工程研究》2018年第5期675-679,共5页Chinese Journal of Tissue Engineering Research

摘　　要：背景:细胞移植后的低存活率是限制细胞治疗效果的一个重要因素,其解决方法之一是用生物材料作为移植细胞的载体。目的:探索透明质酸水凝胶包裹骨髓间充质干细胞对心肌梗死大鼠心功能的影响。方法:分离培养雄性SD大鼠骨髓间充质干细胞,然后用透明质酸水凝胶包裹骨髓间充质干细胞在培养皿中进行体外三维培养。结扎雌性SD大鼠前降支制作大鼠心肌梗死模型,1周后行超声检测,将符合条件的大鼠随机分为4组:①PBS对照组(n=8);②水凝胶组(n=8);③细胞组(n=29);④细胞+水凝胶组(n=29)。造模1周后将模型鼠行二次开胸,按照分组将移植物注射到梗死边缘区及梗死区。移植后1 d和1,2周,RT-PCR评价细胞的存活率,TUNEL检测移植细胞的凋亡率;移植后4周,超声检测心功能。结果与结论:①移植后1 d及2周,细胞+水凝胶组的移植细胞存活率显著高于单纯细胞组(P<0.05);②移植后1 d及1周,细胞+水凝胶组的移植细胞凋亡率显著低于单纯细胞组(P<0.05);③移植后4周,细胞+水凝胶组的心功能显著改善,与其他组比较差异有显著性意义(P<0.05);④结果表明,透明质酸水凝胶提高了移植细胞的存活率,使得心肌梗死部位早期(2周之内)有更多的细胞参与损伤心肌的修复过程,达到了显著改善心功能的效果。BACKGROUND:The poor retention and survival of donor cells implanted into the myocardium limit the efficacy of cell therapy for myocardial infarction.Embedding cells in natural or synthetic biomaterials is a strategy to address this issue.OBJECTIVE:To explore the effects of bone marrow mesenchymal stem cells(BMSCs)encapsulated in hyaluronic acid(HA)hydrogel on cardiac function after myocardial infarction.METHODS:BMSCs from male Sprague-Dawley rats were isolated and cultured,and then HA-encapsulated BMSCs were cultured in vitro in the three-dimensional manner.A model of myocardial infarction was made by cutting the anterior descending artery of female Sprague-Dawley rats.After 1 week,the model rats were screened by ultrasonic testing and then eligible ones were randomly divided into four groups:PBS group(n=8),HA group(n=8),BMSCs group(n=29),and HA-encapsulated BMSCs group(n=29).At 1 week after modeling,the model rats underwent the secondary thoracotomy and the implants were injected into the marginal zone and infarcted region in corresponding groups.The survival rate and apoptosis of implanted cells were examined at post-injection day 1,week 1 and week 2 by RT-PCR and TUNEL respectively.At post-injection week 4,changes of cardiac microstructure and function were evaluated by histological examination and echocardiography.RESULTS AND CONCLUSION:Compared with the BMSCs group,HA hydrogel significantly enhanced the survival rate and reduced the apoptotic rate of BMSCs at post-injection day 1 and week 2(both P<0.05).At post-injection week 4,the HA+BMSCs combined treatment yielded the best recovery of cardiac function(P<0.05).To conclude,HA hydrogel can act as a vehicle for BMSCs delivery and improve the beneficial effects of implanted BMSCs in early myocardial repair(within 2 weeks after infarction)via enhancing cell retention and survival.

关 键 词：透明质酸 骨髓间充质干细胞 心肌梗死 细胞移植 心功能 干细胞 

分 类 号：R394.2[医药卫生—医学遗传学]