Research and Development Unit, National Heart Center Singapore, Singapore, Singapore.
Tissue Eng Part A. 2012 Aug;18(15-16):1652-63. doi: 10.1089/ten.TEA.2011.0591. Epub 2012 Jun 25.
Tissue-engineered scaffolds may improve experimental outcomes in cardiac cell therapy by targeted delivery of stem cells and mechanically support an infarcted left ventricular (LV) wall. We transplanted cardiomyocyte-like cells (5×10(5)) with scaffolding via epicardial patching (cell patch, n=17) or a low-dose intramyocardial hydrogel (LD hydrogel, n=18), a high-dose (5×10(6)) intramyocardial hydrogel (HD hydrogel, n=18) or transplanting a serum-free medium control (control, n=13), a blank patch (n=14), and a blank gel (n=16) for targeted cardiomyoplasty in a myocardial infarcted rat model. LV real-time hemodynamics were assessed using a 1.9-F pressure-volume catheter 7 weeks after stem cell transplantation. All mode of scaffold transplantation protected diastolic function by preserving LV wall integrity that resulted in a lower end diastolic pressure-volume relationship (EDPVR) as compared to a control medium-injected group. Moreover, epicardial patching, but not hydrogel injection, reduced ventricular wall stress with a significantly better LV end diastolic pressure (EDP: 5.3±2.4 mmHg vs. 9.6±6.9 mmHg, p<0.05) as compared to control. Furthermore, epicardial patching additionally preserved systolic function by modulating negative remodeling through restricting dilatation of the LV chamber. In comparison to control, an improved ejection fraction in the cell patch group (80.1%±5.9% vs. 67.9%±3.2%, p<0.01) was corroborated by load-independent enhancement of the end systolic pressure-volume relationship (ESPVR: 0.88±0.61 mmHg/uL vs. 0.29±0.19 mmHg/uL, p<0.05) and preload recruitable stroke work (PRSW: 68.7±26.4 mmHg vs. 15.6±16.2 mmHg, p<0.05) in systolic function. Moreover, the cell patch group (14.2±1.7 cells/high-power field vs. 7.4±1.6 cells/high power field, p<0.05) was significantly better in myocardial retention of transplanted stem cells as compared to the LD hydrogel group. Collectively, myocardial transplantation of compliant scaffolding materials alone may physically improve wall mechanics, largely independent of stem cells. However, epicardially grafted cell patch conferred added systolic contractility by improving stem cell retention and cellular alignment leading to improved LV remodeling and geometric preservation postinfarction.
组织工程支架可以通过靶向递送干细胞和机械支撑梗死的左心室（LV）壁来改善心脏细胞治疗的实验结果。我们通过心外膜贴片（细胞贴片，n=17）或低剂量心肌内水凝胶（LD 水凝胶，n=18）、高剂量（5×10（6））心肌内水凝胶（HD 水凝胶，n=18）或移植无血清培养基对照（对照，n=13）、空白贴片（n=14）和空白凝胶（n=16）将心肌细胞样细胞（5×10（5））与支架一起移植到心肌梗死大鼠模型中进行靶向心肌成形术。干细胞移植后 7 周，使用 1.9-F 压力-容积导管评估 LV 实时血液动力学。与对照组相比，所有支架移植方式均通过维持 LV 壁完整性来保护舒张功能，从而降低舒张末期压力-容积关系（EDPVR）。此外，与对照组相比，心外膜贴片移植而非水凝胶注射降低了心室壁应力，LV 舒张末期压力明显更低（EDP：5.3±2.4mmHg 比 9.6±6.9mmHg，p<0.05）。此外，心外膜贴片还通过限制 LV 腔扩张来调节负性重构，从而进一步维持收缩功能。与对照组相比，细胞贴片组的射血分数得到改善（80.1%±5.9%比 67.9%±3.2%，p<0.01），并且通过独立于负荷的收缩末期压力-容积关系（ESPVR：0.88±0.61mmHg/μL 比 0.29±0.19mmHg/μL，p<0.05）和预负荷可获取的收缩功（PRSW：68.7±26.4mmHg 比 15.6±16.2mmHg，p<0.05）得到改善。此外，与 LD 水凝胶组相比，细胞贴片组（14.2±1.7 个细胞/高倍视野比 7.4±1.6 个细胞/高倍视野，p<0.05）的移植干细胞在心肌中的保留情况更好。总的来说，单独移植顺应性支架材料可能在很大程度上通过改善壁力学来改善心肌功能，而与干细胞无关。然而，心外膜移植的细胞贴片通过改善干细胞保留和细胞排列来增加收缩力，从而改善梗死后的 LV 重塑和几何形状保存。
