Intramyocardial Peptide Nanofiber Injection Improves Postinfarction Ventricular Remodeling and Efficacy of Bone Marrow Cell Therapy in Pigs
Intramyocardial Peptide Nanofiber Injection Improves Postinfarction Ventricular Remodeling and Efficacy of Bone Marrow Cell Therapy in Pigs
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DOI：
10.1161/circulationaha.110.939512
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发表时间：
2010-09-14
期刊：
影响因子：
37.8
通讯作者：
Hsieh, Patrick C. H.
中科院分区：
文献类型：
--
作者：
Lin, Yi-Dong;Yeh, Ming-Long;Hsieh, Patrick C. H.
背景-越来越多的证据表明心肌内注射生物材料可改善啮齿动物心肌梗死（MI）后的心脏功能。细胞疗法是治疗MI的另一种有希望的方法，尽管移植细胞的保留差是一个主要挑战。在这项研究中，我们假设，心肌内注射自组装肽纳米纤维（NFs）增厚梗死心肌，增加移植自体骨髓单个核细胞（MNC）保留，以减轻心脏重塑和功能障碍，在猪MI model.Methods和Results-A共40成熟的小型猪分为5组：假手术，MI+生理盐水，MI+NFs，MI+ MNC，MI+ MNC/NFs。通过冠状动脉闭塞，随后心肌内注射2 mL生理盐水或1% NF（含或不含1 × 10（8）个分离的自体MNC）诱导MI。治疗后28天，NF注射液显著改善舒张功能，减少心室重构。单独注射MNCs仅改善收缩功能，而注射MNCs和NF显著改善收缩和舒张功能，如+dP/dt和-dP/dt所示（MI+NS分别为1214.5 +/- 91.9和-1109.7 +/- 91.2 mmHg/s，MI+ MNC/NF分别为1693.7 +/- 84.7和-1809.6 +/- 264.3 mmHg/s），增加移植细胞滞留（MI+MNCs为29.3 +/- 4.5 cells/mm（2），MI+ MNCs/NF为229.4 +/- 41.4 cells/mm（2）），并促进了梗死区的毛细血管密度。而在猪MI后，植入NF的细胞可改善细胞滞留和心脏功能。在大型动物模型中进行的这种前所未有的联合治疗具有治疗效果，可以在可预见的未来转化为临床应用。（循环。2010; 122[suppl 1]：S132-S141.）
Background-Growing evidence suggests that intramyocardial biomaterial injection improves cardiac functions after myocardial infarction (MI) in rodents. Cell therapy is another promising approach to treat MI, although poor retention of transplanted cells is a major challenge. In this study, we hypothesized that intramyocardial injection of self-assembling peptide nanofibers (NFs) thickens the infarcted myocardium and increases transplanted autologous bone marrow mononuclear cell (MNC) retention to attenuate cardiac remodeling and dysfunction in a pig MI model.Methods and Results-A total of 40 mature minipigs were divided into 5 groups: sham, MI+ normal saline, MI+NFs, MI+MNCs, and MI+MNCs/NFs. MI was induced by coronary occlusion followed by intramyocardial injection of 2 mL normal saline or 1% NFs with or without 1 X 10(8) isolated autologous MNCs. NF injection significantly improved diastolic function and reduced ventricular remodeling 28 days after treatment. Injection of MNCs alone ameliorated systolic function only, whereas injection of MNCs with NFs significantly improved both systolic and diastolic functions as indicated by +dP/dt and -dP/dt (1214.5 +/- 91.9 and -1109.7 +/- 91.2 mm Hg/s in MI+NS, 1693.7 +/- 84.7 and -1809.6 +/- 264.3 mm Hg/s in MI+MNCs/NFs, respectively), increased transplanted cell retention (29.3 +/- 4.5 cells/mm(2) in MI+MNCs and 229.4 +/- 41.4 cells/mm(2) in MI+ MNCs/NFs) and promoted capillary density in the pen-infarct area.Conclusions-We demonstrated that NF injection alone prevents ventricular remodeling, whereas cell implantation with NFs improves cell retention and cardiac functions after MI in pigs. This unprecedented combined treatment in a large animal model has therapeutic effects, which can be translated to clinical applications in the foreseeable future. (Circulation. 2010; 122[suppl 1]:S132-S141.)