A tissue engineering approach to progenitor cell delivery results in significant cell engraftment and improved myocardial remodeling
A tissue engineering approach to progenitor cell delivery results in significant cell engraftment and improved myocardial remodeling
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DOI：
10.1634/stemcells.2007-0132
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发表时间：
2007-09-01
期刊：
影响因子：
5.2
通讯作者：
Dudley, Samuel C., Jr.
中科院分区：
文献类型：
--
作者：
Simpson, David;Liu, Hong;Dudley, Samuel C., Jr.
细胞替代疗法已成为心肌修复的一种有吸引力的解决方案。然而，典型的细胞递送技术遭受差的细胞移植和不均匀的细胞分布。因此，我们评估了一个假设，即心外膜应用，组织工程心脏补丁含有祖细胞将导致增强外源性细胞植入。将人骨髓间充质干细胞（hMSCs）包埋到大鼠尾I型胶原基质中以形成心脏补片。通过结扎免疫活性的雄性剖腹产fischer大鼠的冠状动脉左前降支诱导心肌梗死，用纤维蛋白密封剂将含或不含细胞的补片固定在心脏上。在贴片形成后，hMSC在培养中5天内保持>90%的活力。此外，>75%的hMSC在贴片植入之前保持高度的效力。培养4天后，将贴片应用于梗塞区域的心外膜表面，并在1周时导致23%+/-4%的hMSC植入（n = 6）。补片应用导致收缩期左心室内径减小，前壁厚度增加，缩短分数增加30%。尽管在心肌重塑方面有这种改善，但在贴片应用后4周时未检测到hMSC，这意味着改善不需要长期的细胞植入。没有祖细胞的贴片在重塑方面没有改善。总之，使用心外膜心脏补片可以将多能hMSC有效地递送到心肌损伤部位，并且这种递送导致梗死后心肌重塑的改善。
Cell replacement therapy has become an attractive solution for myocardial repair. Typical cell delivery techniques, however, suffer from poor cell engraftment and inhomogeneous cell distributions. Therefore, we assessed the hypothesis that an epicardially applied, tissue-engineered cardiac patch containing progenitor cells would result in enhanced exogenous cell engraftment. Human mesenchymal stem cells (hMSCs) were embedded into a rat tail type I collagen matrix to form the cardiac patch. Myocardial infarction was induced by left anterior descending coronary artery ligation in immunocompetent male cesarean-derived fischer rats, and patches with or without cells were secured to hearts with fibrin sealant. After patch formation, hMSCs retained a viability of >90% over 5 days in culture. In addition, >75% of hMSCs maintained a high degree of potency prior to patch implantation. After 4 days in culture, patches were applied to the epicardial surface of the infarct area and resulted in 23%+/-4% engraftment of hMSCs at 1 week (n = 6). Patch application resulted in a reduction in left ventricle interior diameter at systole, increased anterior wall thickness, and a 30% increase in fractional shortening. Despite this improvement in myocardial remodeling, hMSCs were not detectable at 4 weeks after patch application, implying that improvement did not require long-term cell engraftment. Patches devoid of progenitor cells showed no improvement in remodeling. In conclusion, pluripotent hMSCs can be efficiently delivered to a site of myocardial injury using an epicardial cardiac patch, and such delivery results in improved myocardial remodeling after infarction.