Repair of impaired myocardium by means of implantation of engineered autologous myoblast sheets
Repair of impaired myocardium by means of implantation of engineered autologous myoblast sheets
复制标题
DOI：
10.1016/j.jtcvs.2005.07.023
复制
发表时间：
2005-11-01
影响因子：
6
通讯作者：
Matsuda, H
中科院分区：
文献类型：
--
作者：
Memon, IA;Sawa, Y;Matsuda, H
目的：通过注射方法进行的自体骨骼肌成肌细胞移植易遭受细胞间通讯、细胞外基质和细胞数量的损失。我们假设骨骼肌成肌细胞片的植入可能在修复受损的心脏中更有利，因为它提供了均匀和稳定的细胞递送，细胞损失更少，并且不破坏细胞-细胞微环境。结扎冠状动脉左前降支的刘易斯大鼠心脏（2周，共173例）通过成肌细胞注射或植入2个单层构建的成肌细胞片的细胞移植接受1 × 107个自体骨骼肌成肌细胞（5 X IO6个细胞/片）或通过培养基注射。成肌细胞片与温度响应，聚合物移植的细胞培养皿，释放融合的细胞从培养皿表面在小于20摄氏度。结果：超声心动图结果表明，更高的改善，心脏性能的成肌细胞片组比其他组之间，直到细胞移植后8周。组织学比较显示，仅在成肌细胞片组心脏中，在明显均匀增厚的壁内存在更大的细胞结构和丰富的广泛的新包膜。与骨骼肌成肌细胞注射相比，骨骼肌成肌细胞片植入显著减少了纤维化。在成肌细胞片组梗死心脏区域观察到明显较高数量的造血干细胞（c-kit、干细胞抗原1和CD 34）。逆转录聚合酶链反应结果显示，基质衍生因子1，肝细胞生长因子，血管内皮生长因子的表达如下：成肌细胞片>成肌细胞注射> control.Conclusions：成肌细胞片修复受损的心肌，减少纤维化，并防止重塑与招募造血干细胞通过释放基质衍生因子I和其他生长因子。我们的实验为严重心力衰竭患者提供了一种治疗方法。
Objectives: Autologous skeletal myoblast cell transplantation by means of the injection method is subject to the loss of intercellular communication, extracellular matrix, and cell numbers. We hypothesize that the implantation of skeletal myoblast cell sheets might be more advantageous in repairing the impaired heart by providing uniform and stable cell delivery with less cell loss and without disrupting the cell-cell microenvironment.Methods: Left anterior descending coronary artery-ligated Lewis rat hearts (2 weeks, total n = 173) received I X 107 autologous skeletal myoblasts by means of cell transplantation either through myoblast injection or implantation of 2 monolayer-constructed myoblast sheets (5 X 106 cells per sheet) or through medium injection. Myoblast sheets were constructed with temperature-responsive, polymer-grafted cell-culture dishes, which release the confluent cells from the dish surface at less than 20 degrees C.Results: Echocardiographic results indicated higher improvement of cardiac performance in the myoblast sheet group than among the other groups until 8 weeks after cell transplantation. Histologic comparison revealed greater cellularity and abundant widespread neocapillaries within the noticeable uniform thickened wall in myoblast sheet group hearts only. Fibrosis was substantially reduced with skeletal myoblast sheet implantation compared with skeletal myoblast cell injection. Obviously higher numbers of hematopoietic stern cells (c-kit, stem cell antigen 1, and CD34) were observed in the myoblast sheet group infarct heart region. Reverse transcriptionpolymerase chain reaction results showed expression of stromal-derived factor 1, hepatocyte growth factor, and vascular endothelial growth factor as follows: myoblast sheets > myoblast injection > control.Conclusions: Myoblast sheets repaired the impaired myocardium, reduced fibrosis, and prevented remodeling in association with recruitment of hematopoietic stem cells through the release of stromal-derived factor I and other growth factors. Our experiment indicates a therapy for patients with severe heart failure.