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多孔多糖基支架介导间充质干细胞移植治疗大鼠梗死心肌:与心内膜注射的定量比较。

Mesenchymal stem cell delivery into rat infarcted myocardium using a porous polysaccharide-based scaffold: a quantitative comparison with endocardial injection.

机构信息

Inserm, U698, Bio-ingénierie Cardiovasculaire, Universities Paris 7 and Paris 13, Hôpital Bichat, Paris, France.

出版信息

Tissue Eng Part A. 2012 Jan;18(1-2):35-44. doi: 10.1089/ten.TEA.2011.0053. Epub 2011 Sep 21.

Abstract

The use of mesenchymal stem cells (MSCs) for tissue regeneration is often hampered by modest engraftment in host tissue. This study was designed to quantitatively compare MSCs engraftment rates after delivery using a polysaccharide-based porous scaffold or endocardial (EC) injection in a rat myocardial infarction model. Cellular engraftment was measured by quantitative reverse transcription-polymerase chain reaction using MSCs previously transduced with a lentiviral vector that expresses green fluorescent protein (GFP). The use of a scaffold promoted local cellular engraftment and survival. The number of residual GFP(+) cells was greater with the scaffold than after EC injection (9.7% vs. 5.1% at 1 month and 16.3% vs. 6.1% at 2 months, respectively [n=5]). This concurred with a significant increase in mRNA vascular endothelial growth factor level in the scaffold group (p<0.05). Clusters of GFP+ cells were detected in the peri-infarct area, mainly phenotypically consistent with immature MSCs. Functional assessment by echocardiography at 2 months postinfarct also showed a trend toward a lower left ventricular dilatation and a reduced fibrosis in the scaffold group in comparison to direct injection group (n=10). These findings demonstrate that using a porous biodegradable scaffold is a promising method to improve cell delivery and engraftment into damaged myocardium.

摘要

间充质干细胞(MSCs)在组织再生中的应用常因在宿主组织中的移植率较低而受到限制。本研究旨在通过定量逆转录聚合酶链反应,比较多糖基多孔支架或心内膜(EC)注射在大鼠心肌梗死模型中输送后 MSCs 移植率。使用先前转导有绿色荧光蛋白(GFP)的慢病毒载体的 MSCs 进行细胞移植。支架的使用促进了局部细胞移植和存活。支架组的 GFP(+)细胞残留数量多于 EC 注射组(1 个月时分别为 9.7%和 5.1%,2 个月时分别为 16.3%和 6.1%,n=5)。这与支架组中血管内皮生长因子 mRNA 水平的显著增加相一致(p<0.05)。在梗死周边区检测到 GFP+细胞簇,主要表型与未成熟的 MSCs 一致。与直接注射组相比(n=10),在梗死 2 个月后进行超声心动图功能评估也显示出支架组左心室扩张程度较低和纤维化程度较低的趋势。这些发现表明,使用多孔可生物降解支架是一种有前途的方法,可以提高细胞输送和移植到受损心肌中的效率。

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