心表移植源自自体骨髓干细胞的生物工程学人造组织,改善大鼠梗死区域的心肌灌注(英文)

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

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-MIBISPECT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补片及相邻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±76vs89±21;P=0.01)和(1.75±0.24vs1.35±0.31;P=0.04)。序列99mTc-MIBISPECT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%vs20%±12.9%;P=0.02)和(65%±17%vs52%±12%;P=0.04)。但两组的LVEF均值无明显差异。结论在这项研究中,我们确认在植入大鼠体内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 marrow stem ceils （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） models were 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 performed for all animals at 2 weeks before and 2 months after the graft experiment, to monitor the evolution of left vantricular （LV） function and myocardial perfusion. The hearts were harvested at the end of study for histological analysis, to investigate the fate of BMSCs in bioengineered tissue graft. [Results] Two months later, histological studies 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 myoeardium, the capillary density per square millimeter and the thickness of the infarcted left ventricular wall in AT graft treated rats was significantly augmented compared with untreated rats, [（246±76） vs （89±21）; P=0.01] and [（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 augmentation of ^99mTc-Sestamibi uptake rate, compared with the control group, [（10%±7.1%） vs （20%±12.9%）; P =0.02] and [（65%± 17%） vs （52%±12%）; P =0.04]. But the mean value of LVEF had no significant difference between the two groups. [Conclusion] In this study, we confirm that epicardial grafted artificial tissue bioengineered with autologous BMSCs could integrate with infarcted myocardium, introduce neo-angiogenesis and significantly improve the regional myocardial peffusion but not the LV function,2 months after it was implanted in rats.