心表移植源自自体骨髓干细胞的人造组织与大鼠梗死区域心肌的作用  

Epicardial graft of artificial tissue bioengineered with autologous bone marrow stem cells improves regional perfusion of infarcted myocardium in rat

作　　者：李岩[1] 宋波[1] 李西慧[1] 王进[1] 杨阳[1] 肖锋[1] 张明礼[1] 

机构地区：[1]北京大学第一医院心血管外科,北京100034

出　　处：《中国医学工程》2008年第4期241-244,248,共5页China Medical Engineering

基　　金：教育部教育振兴行动计划专项基金(985工程)资助

摘　　要：目的探究源自自体骨髓干细胞(BMSCs)的生物工程学人造组织(AT)作为组织补片被移植在大鼠的梗死心肌表面上后,能否与受损心肌完全一体化融合。方法对15只Wister大鼠进行选择性冠状动脉结扎以建立心肌梗死(MI)动物模型,将大鼠自体BMSCs植入胶原蛋白基质以构建三维立体AT。4周后,AT补片被移植在移植组大鼠(n=9)心脏的MI瘢痕区表面,对照组(n=6)不做移植。所有动物在移植实验2周前和2个月后进行序列99mTc-MIBI SPECT心肌灌注显像,以检测左心室(LV)功能和心肌灌注的演变。在研究终点切取大鼠心脏进行组织学分析,以研究生物工程学组织移植物中BMSCs的命运。结果2个月后,在移植组中,组织学分析显示生物工程学AT移植物中的BMSCs存活并与MI瘢痕组织完全一体化,在AT补片及相临梗死心肌中出现大量新生毛细血管,其每平方毫米的毛细血管密度及梗死区的左心室壁厚度显著大于对照组[(246±76)vs(89±21);P=0.01]和[(1.75±0.24)vs(1.35±0.31);P=0.04]。序列99mTc-MIBI SPECT心肌灌注显像显示移植组心肌局部灌注得到明显改善,与对照组相比,移植组的低灌注MI区显著减少而99mTc-Sestamibi摄取率显著增加,[(10%±7.1%)vs(20%±12.9%);P=0.02]和[(65%±17%)vs(52%±12%);P=0.04]。但两组的LVEF均值差异无显著性。结论在植入大鼠体内2个月后,心表移植的源自自体BMSCs的生物工程学人造组织可以与梗死心肌完全融合,促进新血管生成并显著改善局部灌注,但并不改善LV功能。【Objective】To investigate whether the artificial tissue (AT) bioengineered with autologous bone mar-row stem cells (BMSCs) could integrate with the damaged myocardium after it was epicardially grafted as a tissue patch on the infarcted myocardium in rat. 【Methods】Myocardial infarction (MI) model was created in 15 Wister rats with selective coronary artery ligature,3-dimensional AT was constructed by seeding autologous rat BMSCs to collagen matrix. Four weeks later,AT patch was epicardially grafted on the scar area of MI for rats from graft group (n =9),but not for rats from control group (n =6). Serial 99mTc-MIBI SPECT myocardial perfusion imaging was per-formed for all the animals at 2 weeks before and 2 months after the graft experiment,to monitor the evolution of left ventricular (LV) function and myocardial perfusion. The hearts were harvested at the end of study for histological analyses,to investigate the fate of BMSCs in bioengineered tissue graft. 【Result】Two months later,histologicalstudies showed that BMSCs in bioengineered AT graft survived and completely incorporated with the scar tissue of MI,enhanced neo-angiogenesis was detected in the AT patch and adjacent infarcted myocardium,the capillary den-sity per square millimeter and the thickness of the infarcted left ventricular wall in AT graft treated rats were signifi-cantly augmented compared with un-treated rats,[(246±76) vs (89±21),P =0.01]; [(1.75±0.24) vs (1.35±0.31),P=0.04]. Furthermore,the serial 99mTc-MIBI-SEPCT study revealed an obvious improvement of regional myocardial perfusion in rats from graft group,with a significant reduction of under-perfused MI area and a significant augmen-tation of 99mTc-Sestamibi uptake rate,compared with the control group,[(10%±7.1%) vs (20%±12.9%); P =0.02; (65%±17%) vs (52%±12%),P =0.04]. But the mean value of LVEF had no significant difference between two groups. 【Conclusion】Epicardial grafted artificial tissue bioengineered with autologous BMSCs could integrate with infarcted myocardi

关 键 词：人造组织移植物 生物工程学 骨髓干细胞 心肌梗死 新生血管 

分 类 号：R542.22[医药卫生—心血管疾病]