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经门静脉移植脂肪间充质干细胞可改善 CCl4 诱导的大鼠肝纤维化的微循环。

Adipose derived mesenchymal stem cells transplantation via portal vein improves microcirculation and ameliorates liver fibrosis induced by CCl4 in rats.

机构信息

Department of Interventional Oncology, the First Affiliated Hospital of Sun Yat-sen University, No. 58, Zhongshan 2nd Road, Guangzhou 510080, China.

出版信息

J Transl Med. 2012 Jun 26;10:133. doi: 10.1186/1479-5876-10-133.

DOI:10.1186/1479-5876-10-133
PMID:22735033
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3439354/
Abstract

INTRODUCTION

Adipose derived mesenchymal stem cells (ADMSCs), carrying the similar characteristics to bone marrow mesenchymal stem cells, only much more abundant and easier to obtain, may be a promising treatment for liver fibrosis. We aim to investigate the therapeutic potential of ADMSCs transplantation in liver fibrosis caused by carbon tetrachloride (CCl4) in rats as well as its underlying mechanism, and to further explore the appropriate infusion pathway.

METHODS

ADMSCs were isolated, cultured and identified. Placebo and ADMSCs were transplanted via portal vein and tail vein respectively into carbon tetrachloride (CCl4)-induced liver fibrosis rats. Computed tomography (CT) perfusion scan and microvessel counts were performed to measure the alteration of liver microcirculation after therapy. Liver function tests and histological findings were estimated.

RESULTS

CT perfusion scan shown significant decrease of hepatic arterial perfusion index, significant increased portal vein perfusion, total liver perfusion in rats receiving ADMSCs from portal vein, and Factor VIII (FVIII) immunohistochemical staining shown significant decrease of microvessels in rats receiving ADMSCs from portal vein, indicating microcirculation improvement in portal vein group. Vascular endothelial growth Factor (VEGF) was significantly up-regulated in fibrosis models, and decreased after ADMSCs intraportal transplantation. A significant improvement of liver functional test and histological findings in portal vein group were observed. No significance was found in rats receiving ADMSCs from tail vein.

CONCLUSIONS

ADMSCs have a therapeutic effect against CCl4-mediated liver fibrosis. ADMSCs may benefit the fibrotic liver through alteration of microcirculation, evidenced by CT perfusion scan and down-regulation of VEGF. Intraportal transplantation is a better pathway than tail vein transplantation.

摘要

简介

脂肪间充质干细胞(ADMSCs)具有与骨髓间充质干细胞相似的特征,但数量更多,更容易获得,可能是治疗肝纤维化的一种很有前途的方法。我们旨在研究 ADMSCs 移植治疗四氯化碳(CCl4)诱导的大鼠肝纤维化的治疗潜力及其潜在机制,并进一步探讨合适的输注途径。

方法

分离、培养和鉴定 ADMSCs。分别通过门静脉和尾静脉将安慰剂和 ADMSCs 移植到四氯化碳(CCl4)诱导的肝纤维化大鼠中。通过计算机断层扫描(CT)灌注扫描和微血管计数来测量治疗后肝脏微循环的变化。评估肝功能试验和组织学发现。

结果

CT 灌注扫描显示,门静脉组大鼠肝动脉灌注指数显著降低,门静脉灌注显著增加,总肝灌注增加,VIII 因子(FVIII)免疫组织化学染色显示门静脉组大鼠微血管显著减少,表明门静脉组微血管循环改善。血管内皮生长因子(VEGF)在纤维化模型中显著上调,ADMSCs 门静脉移植后下调。门静脉组大鼠肝功能试验和组织学发现有显著改善。尾静脉组未见明显改善。

结论

ADMSCs 对 CCl4 介导的肝纤维化具有治疗作用。ADMSCs 通过改变 CT 灌注扫描和下调 VEGF 来改善纤维化肝脏的微循环,从而发挥有益作用。门静脉移植比尾静脉移植更具优势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f27/3439354/76e60a5d0f42/1479-5876-10-133-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f27/3439354/80b16f5325ad/1479-5876-10-133-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f27/3439354/d12b14cf2c12/1479-5876-10-133-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f27/3439354/fa0e126e0347/1479-5876-10-133-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f27/3439354/76e60a5d0f42/1479-5876-10-133-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f27/3439354/80b16f5325ad/1479-5876-10-133-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f27/3439354/d12b14cf2c12/1479-5876-10-133-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f27/3439354/fa0e126e0347/1479-5876-10-133-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f27/3439354/76e60a5d0f42/1479-5876-10-133-4.jpg

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