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使用附有大网膜瓣的细胞片层的新型再生疗法在猪心肌梗死模型中输送大量细胞。

Novel regenerative therapy using cell-sheet covered with omentum flap delivers a huge number of cells in a porcine myocardial infarction model.

机构信息

Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

出版信息

J Thorac Cardiovasc Surg. 2011 Nov;142(5):1188-96. doi: 10.1016/j.jtcvs.2011.07.002. Epub 2011 Sep 14.

DOI:10.1016/j.jtcvs.2011.07.002
PMID:21924436
Abstract

OBJECTIVE

A key challenge to applying cell transplantation to treat severely damaged myocardium is in delivering large numbers of cells with minimum cell loss. We developed a new implantation method using skeletal myoblast (SMB) sheets, wrapped with an omentum flap as a blood supply to deliver huge numbers of SMBs to the damaged heart. We examined whether this method could be used to deliver a large amount of cells to deteriorated porcine myocardium.

METHODS

Cell sheets were obtained by culturing mini-pig autologous SMB cells on temperature-responsive culture dishes. Myocardial infarction was induced by placing an ameroid constrictor around the left anterior descending artery. The mini-pigs were divided into 4 treatment groups (n = 6 in each): cell sheets with omentum, cell sheets only, omentum only, and sham operation. Each animal implant consisted of 30 cell sheets (1.5 × 10(7) cells per sheet). Six 5-layer constructs were each placed on a different area, immediately adjacent to but not overlapping one another, to cover the infarct and border regions.

RESULTS

The new regenerative cell delivery system using SMB sheets covered and wrapped with omentum resulted in (1) a significantly reduced infarct size causing, at least in part, a thin scar with thick well-vascularized cardiac tissue; (2) increased angiogenesis, as determined by a significantly higher vascular density; and (3) improved cardiac function, as determined by echocardiography, compared with the conventional method (SMB sheet implantation).

CONCLUSIONS

This cell delivery system shows potential for repairing the severely failed heart.

摘要

目的

将细胞移植应用于治疗严重受损心肌的一个关键挑战是如何输送大量细胞且最小化细胞损失。我们开发了一种新的植入方法,使用骨骼肌母细胞 (SMB) 片,包裹在大网膜瓣中作为血液供应,将大量 SMB 输送到受损的心脏。我们研究了这种方法是否可用于向恶化的猪心肌输送大量细胞。

方法

通过在温度响应培养皿上培养迷你猪自体 SMB 细胞获得细胞片。通过在左前降支周围放置 ameroid 缩窄器诱导心肌梗死。将迷你猪分为 4 个治疗组(每组 n = 6):带大网膜的细胞片、仅细胞片、仅大网膜和假手术。每个动物植入物由 30 个细胞片组成(每个细胞片 1.5 × 10(7)个细胞)。将 6 个 5 层结构分别放置在不同的区域,彼此相邻但不重叠,以覆盖梗死区和边缘区。

结果

使用 SMB 片覆盖和包裹大网膜的新型再生细胞输送系统导致:(1)梗死面积显著减小,至少部分导致薄疤痕,伴有厚且血管丰富的心脏组织;(2)血管密度显著升高,表明血管生成增加;(3)与传统方法(SMB 片植入)相比,超声心动图显示心功能得到改善。

结论

这种细胞输送系统显示出修复严重衰竭心脏的潜力。

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