脂肪间充质干细胞复合多孔壳聚糖微球修复大鼠肝损伤  

Repair of liver injury in rats by adipose-derived mesenchymal stem cells combined with porous chitosan microspheres

作　　者：黄坤 刘承利[1,2] 韩公海[3,4] 刘锐[1,2] 陈伟伟 丁晓[3] 汤贺[3] 彭江 Huang Kun;Liu Chengli;Han Gonghai;Liu Rui;Chen Weiwei;Ding Xiao;Tang He;Peng Jiang(Clinical Medical College of Air Force, Anhui Medical University, Hefei 230032, Anhui Province, China;Air Force General Hospital of PLA, Beijing 100142, China;PLAInstitute of Orthopedics, PLA General Hospital, Beijing 100853, China;Kunming Medical University, Kunming 650500, Yunnan Province,China)

机构地区：[1]安徽医科大学空军临床学院,安徽省合肥市230032 [2]中国人民解放军空军总医院,北京市100142 [3]中国人民解放军总医院全军骨科研究所,北京市100853 [4]昆明医科大学,云南省昆明市650500

出　　处：《中国组织工程研究》2019年第5期716-722,共7页Chinese Journal of Tissue Engineering Research

基　　金：解放军总医院转化医学项目(2016TM-020);项目负责人:彭江~~

摘　　要：背景:随着干细胞治疗及组织工程的发展,利用生物相容性好的生物高分子材料结合脂肪间充质干细胞构建肝脏组织工程微单元成为治疗肝脏疾病的新策略。目的:探讨脂肪间充质干细胞复合多孔壳聚糖微球对急性肝损伤的修复能力。方法:将SD乳鼠脂肪间充质干细胞与多孔壳聚糖微球在体外复合培养,分别在培养第1,3,5天观察细胞在微球上增殖情况。取36只SD大鼠(北京市维通利华实验技术有限公司提供),随机分为3组(n=12):空白对照组,腹腔注射生理盐水;急性肝损伤组,腹腔注射10%四氯化碳-橄榄油;脂肪间充质干细胞-多孔壳聚糖微球组,腹腔注射10%四氯化碳-橄榄油,于注射后第1天通过手术将脂肪间充质干细胞-多孔壳聚糖微球平铺于肝脏表面。分别于注射后第1,2,3,7天进行大体、血清学及组织学评价。结果与结论:(1)脂肪间充质干细胞与多孔壳聚糖微球复合后第1,3,5天,经过活/死染色观察到细胞可在微球上正常生长(死细胞数量远远少于活细胞数量),且细胞在不断增殖;(2)注射后第1,2,3,7天,脂肪间充质干细胞-多孔壳聚糖微球组的大体形态、肝功能及组织学评价均优于急性肝损伤组,从第3天开始脂肪间充质干细胞-多孔壳聚糖微球组与空白对照组已无明显差异;(3)结果表明,将脂肪间充质干细胞-多孔壳聚糖微球移植入肝脏表面可加速肝损伤的修复。BACKGROUND:With the development of stem cell therapy and tissue engineering,adipose-derived mesenchymal stem cells combined with biocompatible scaffolds have been introduced to constructing liver tissue engineering micro-units as a new strategy for the treatment of liver diseases.OBJECTIVE:To investigate the repairing ability of adipose-derived mesenchymal stem cells combined with porous chitosan microspheres on acute liver injury.METHODS:Adipose-derived mesenchymal stem cells from neonatal Sprague-Dawley rats and porous chitosan microspheres were co-cultured in vitro to observe the proliferation of adipose-derived mesenchymal stem cells on the microspheres on the1^st,3^rd and5^th days.Thirty-six Sprague-Dawley rats(provided by Beijing Vital River Laboratory Animal Technology Co.,Ltd.in China)were randomly divided into three groups(n=12per group):control group was intraperitoneally injected with normal saline;acute liver injury group was intraperitoneally administered with10%carbon tetrachloride-olive oil;and cell-microsphere group was intraperitoneally given10%carbon tetrachloride-olive oil and then adipose-derived mesenchymal stem cells-porous chitosan microspheres were implanted into the liver surface on the1^st day after injection.Gross,serological and histological evaluations were performed on the1^st,2^nd,3^rd and7^th days.RESULTS AND CONCLUSION:Adipose-derived mesenchymal stem cells-porous chitosan microspheres were stained with live/dead staining on the1^st,3^rd and5^th days.The cells grew normally on the microspheres as the number of dead cells was much less than that of living cells,and the cells proliferated continuously over time.The gross score,liver function score and histological score of the cell-microsphere group were higher than those of the acute liver injury group on the1^st,2^nd,3^rd and7^th days.There was no significant difference between the cell-microsphere group and control group since the3^rd day.All these experimental findings indicate that adipose-derived mesenchymal stem cells-porous

关 键 词：肝损伤 脂肪间充质干细胞 壳聚糖 四氯化碳 肝功能 肝脏修复 肝疾病 脂肪组织 间质干细胞 组织工程 

分 类 号：R459.9[医药卫生—治疗学] R394.2[医药卫生—临床医学]