TNF-α增加骨髓间充质干细胞在缺血组织黏附的可行性探讨  

Feasibility study of TNF-αincreasing bone marrow mesenchymal stem cell migration to ischemic tissues

作　　者：肖琼 王春艳 田铧[3] 索宁[3] 张肇林[4] 扈燕来[3] 田广平[3] 刘执玉[3] 

机构地区：[1]山东中和干细胞工程有限公司,济南250014 [2]龙口市人民医院心内科 [3]山东大学医学院解剖与组织胚胎学研究所 [4]潍坊医学院附属医院电生理科

出　　处：《中华创伤杂志》2012年第4期361-365,共5页Chinese Journal of Trauma

基　　金：国家自然科学基金资助项目（30872523）;山东省自然科学基金资助项目（ZR2009CZ014）

摘　　要：目的探讨TNF-α促进大鼠骨髓间充质干细胞（mesenchymalstemcells，MSCs）向局部损伤组织迁移的可行性。方法将MSCs用不同浓度的TNF-α刺激，检测其表面黏附分子、干细胞标志物的表达率及其与内皮细胞的黏附；制作大鼠自体血栓微粒，建立后肢缺血模型，选取-合适浓度的TNF-α刺激MSCs，移植到后肢缺血损伤的大鼠，计数损伤处MSCs的数目。结果（1）TNF-α刺激24h后，MSCs的血管细胞黏附分子-1（VCAM-1）表达升高，且呈浓度依赖性，而细胞黏附分子-1（ICAM-1）、L-选择素（L-Selectin）、细胞黏附分子缓慢抗原-4（VLA-4）的表达无明显变化；MSCs的标志物表达率没有明显改变；（2）10ng／mlTNF-仅刺激的MSCs与血管内皮细胞黏附能力明显增强；（3）10ng／mlTNF-仅刺激的MSCs移植到大鼠后肢缺血模型后，损伤侧肌组织内MSCs数目明显多于对照组。结论10ng／mlTNF-α短期内能够有效提高MSCs的VCAM-1表达，促进MSCs与血管内皮细胞的黏附及向受损部位迁移，且不影响MSCs的特性。Objective To study the feasibility of TNF-α promoting migration of rat mesenchymal stem cells （MSCs） to local damaged tissues. Methods The MSCs was exposed to TNF-α at different concentrations and the expression rate of surface adhesion molecules and specific markers as well as their adhesion to endothelial cells were detected. Based on the above steps, the MSCs stimulated with the opti- mal concentration of TNF-α were obtained and were injected intravenously to the rats whose hindlimbs experienced ischemia damage. The rats were executed for achieving the muscle samples in the ischemic are- α, which were made into frozen section to count the number of MSCs. Results （ 1 ） Twenty-four hours after the TNF-α stimulation, the expression of adhesion molecule （ VCAM-1 ） of MSCs increased in a concentration-dependent manner, while the expression of adhesion molecules （ ICAM-1, L-Selectin and VLA- 4） of MSCs showed no significant changes. Besides, the expression rate of specific markers of MSCs was also obscure. （2） Exposed to 10 ng/ml TNF-α, MSCs presented an obviously increased ability in adhe- sion to the endothelial cells. （3） MSCs stimulated with 10 ng/ml TNF-α showed a larger number in the ischemia-damaged tissue of rat hindlimbs than that in the control group. Conclusion TNF-α at concentration of 10 ng/ml is effective within a short term in increasing VCAM-1 expression in rat MSCs and promoting the adhesion of MSCs to endothelial cells without affecting their character.

关 键 词：骨髓 干细胞 细胞黏附分子 内皮细胞 大鼠 

分 类 号：R363[医药卫生—病理学]