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羊膜间充质干细胞具有强大的血管生成特性,在治疗后肢缺血方面非常有效。

Amniotic mesenchymal stem cells have robust angiogenic properties and are effective in treating hindlimb ischaemia.

机构信息

Regional Clinical Center, Dong-A University Hospital, 3-1, Dongdaeshin-Dong, Seo-Gu, Busan 602-715, Republic of Korea.

出版信息

Cardiovasc Res. 2012 Mar 1;93(3):525-34. doi: 10.1093/cvr/cvr328. Epub 2011 Dec 12.

Abstract

AIMS

In this study, we aimed to evaluate whether human amniotic mesenchymal stem cells (AMMs) have angio-vasculogenic properties and to determine their therapeutic effects on experimental ischaemia. Although AMMs are a promising source of stem cells, their angio-vasculogenic properties are not fully understood.

METHODS AND RESULTS

We have characterized AMMs by quantitative real-time polymerase chain reaction, Matrigel tube formation assays, and various in vitro endothelial differentiation assays. AMMs expressed significantly higher levels of representative proangiogenic genes, vascular endothelial growth factor-A, angiopoietin-1, hepatocyte growth factor, and fibroblast growth factor-2 (FGF-2) than adipose-derived mesenchymal stem cells. In addition, the anti-apoptotic factor Akt-1 was highly expressed in the AMMs. Cells were directly transplanted into the ischaemic hindlimbs of mice to evaluate their angio-vasculogenic and therapeutic effects. They spontaneously differentiate into vascular-like structures and exhibit endothelial-specific genes and proteins. In an in vivo study on hindlimb ischaemia, implantation of AMMS augmented blood perfusion and capillary density, indicating AMM-augmented neovascularization. The engraftment rate of AMMs was high, and the transplanted AMMs showed vasulogenic potential.

CONCLUSION

AMMs are not only markedly angiogenic but also vasculogenic, thus ameliorating hindlimb ischaemia. Our data suggest that AMMs have considerable therapeutic effects on ischaemic hindlimb through high angiogenic and engraftment abilities.

摘要

目的

本研究旨在评估人羊膜间充质干细胞(AMMs)是否具有血管生成特性,并确定其对实验性缺血的治疗效果。尽管 AMMs 是一种很有前途的干细胞来源,但它们的血管生成特性尚未完全了解。

方法和结果

我们通过定量实时聚合酶链反应、Matrigel 管形成测定和各种体外内皮细胞分化测定来对 AMMs 进行了表征。AMMs 表达了代表促血管生成基因的水平显著高于脂肪来源的间充质干细胞,如血管内皮生长因子-A、血管生成素-1、肝细胞生长因子和碱性成纤维细胞生长因子-2(FGF-2)。此外,抗凋亡因子 Akt-1 在 AMMs 中高度表达。细胞直接移植到缺血性后肢小鼠中,以评估其血管生成和治疗效果。它们自发分化为类似血管的结构,并表达内皮特异性基因和蛋白质。在一项关于后肢缺血的体内研究中,AMMS 的植入增强了血液灌注和毛细血管密度,表明 AMMS 增强了新生血管形成。AMMs 的植入率很高,移植的 AMMs 显示出血管生成潜力。

结论

AMMs 不仅具有明显的血管生成能力,而且具有血管生成特性,从而改善后肢缺血。我们的数据表明,AMMs 通过高血管生成和植入能力对缺血性后肢具有相当大的治疗效果。

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