Association between a cell-seeded collagen matrix and cellular cardiomyoplasty for myocardial support and regeneration.

Miguel Cortes-Morichetti, Giacomo Frati, Olivier Schussler, Jean-Paul Duong Van Huyen, Evelyne Lauret, Jorge A Genovese, Alain F Carpentier, Juan C Chachques
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引用次数: 93

Abstract

The objective of cellular cardiomyoplasty is to regenerate the myocardium using implantation of living cells. Because the extracellular myocardial matrix is deeply altered in ischemic cardiomyopathies, it could be important to create a procedure aiming at regenerating both myocardial cells and the extracellular matrix. We evaluated the potential of a collagen matrix seeded with cells and grafted onto infarcted ventricles. A myocardial infarction was created in 45 mice using coronary artery ligation. Animals were randomly assigned to 4 local myocardial treatment groups. Group I underwent sham treatment (injection of cell culture medium). Group II underwent injection of human umbilical cord blood mononuclear cells (HUCBCs). Group III underwent injection of HUCBCs and fixation onto the epicardium of a collagen matrix seeded with HUCBCs. Group IV underwent fixation of collagen matrix (without cells) onto the infarct. Echocardiography was performed on postoperative days 7 and 45, followed by histological studies. Echocardiography showed that the association between the cell-loaded matrix and the intrainfarct cell implants was the most efficient approach to limiting postischemic ventricular dilation and remodeling. Ejection fraction improved in both cell-treated groups. The collagen matrix alone did not improve left ventricular (LV) function and remodeling. Histology in Group III showed fragments of the collagen matrix thickening and protecting the infarct scars. Segments of the matrix were consistently aligned along the LV wall, and cells were assembled within the collagen fibers in large populations. Intramyocardial injection of HUCBCs preserves LV function following infarction. The use of a cell-seeded matrix combined with cell injections prevents ventricular wall thinning and limits postischemic remodeling. This tissue engineering approach seems to improve the efficiency of cellular cardiomyoplasty and could emerge as a new therapeutic tool for the prevention of adverse remodeling and progressive heart failure.

细胞种子胶原基质与细胞心肌成形术对心肌支持和再生的关系。
细胞心肌成形术的目的是通过植入活细胞使心肌再生。由于心肌细胞外基质在缺血性心肌病中发生了深刻的改变,因此建立一种既能再生心肌细胞又能再生细胞外基质的方法是很重要的。我们评估了将细胞植入胶原基质并移植到梗死心室的潜力。我们用冠状动脉结扎术在45只小鼠身上制造了心肌梗塞。动物随机分为4个局部心肌治疗组。1组采用假治疗(注射细胞培养基)。第二组注射人脐带血单个核细胞(hucbc)。第三组注射hucbc并将其固定在心外膜胶原基质上。IV组将胶原基质(不含细胞)固定在梗死灶上。术后第7天和第45天进行超声心动图检查,随后进行组织学检查。超声心动图显示,细胞负载基质与梗死内细胞植入物之间的关联是限制缺血后心室扩张和重构的最有效方法。两个细胞处理组的射血分数均有改善。单独的胶原基质不能改善左心室功能和重塑。ⅲ组组织学显示胶原基质增厚,保护梗死瘢痕。基质的片段始终沿着左室壁排列,细胞大量聚集在胶原纤维内。心肌内注射hubc可保留梗死后左室功能。使用细胞种子基质结合细胞注射可防止心室壁变薄并限制缺血后重构。这种组织工程方法似乎可以提高细胞心肌成形术的效率,并可能成为预防不良重构和进行性心力衰竭的新治疗工具。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Tissue engineering
Tissue engineering CELL & TISSUE ENGINEERING-BIOTECHNOLOGY & APPLIED MICROBIOLOGY
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