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大鼠慢性肝损伤模型中经脾内注射高密度培养的骨髓细胞预防肝纤维化

Prevention of liver fibrosis by intrasplenic injection of high-density cultured bone marrow cells in a rat chronic liver injury model.

作者信息

Lian Jie, Lu Yang, Xu Peng, Ai Ai, Zhou Guangdong, Liu Wei, Cao Yilin, Zhang Wen Jie

机构信息

Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of China, Shanghai, China.

出版信息

PLoS One. 2014 Sep 25;9(9):e103603. doi: 10.1371/journal.pone.0103603. eCollection 2014.

DOI:10.1371/journal.pone.0103603
PMID:25255097
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4177810/
Abstract

Endothelial progenitor cells (EPCs) from bone marrow have proven to be functional for the prevention of liver fibrosis in chronic liver injury. However, expansion of EPCs in culture is complicated and expansive. Previously, we have established a simple method that could enrich and expand EPCs by simple seeding bone marrow cells in high density dots. The purpose of this study is to evaluate whether cells derived from high-density (HD) culture of rat bone marrow cells could prevent the liver fibrosis in a chronic liver injury rat model, induced by carbon tetrachloride (CCl4). Flow cytometric analysis showed that cells from HD culture were enriched for EPCs, expressing high levels of EPC markers. Intrasplenic injection of HD cultured bone marrow cells in the CCl4-induced liver injury rat showed an enhanced antifibrogenic effect compared with animals treated with cells from regular-density culture. The antifibrogenic effect was demonstrated by biochemical and histological analysis 4 weeks post-transplantation. Furthermore, cells from HD culture likely worked through increasing neovascularization, stimulating liver cell proliferation, and suppressing pro-fibrogenic factor expression. HD culture, which is a simple and cost-effective procedure, could potentially be used to expand bone marrow cells for the treatment of liver fibrosis.

摘要

骨髓来源的内皮祖细胞（EPCs）已被证明在预防慢性肝损伤中的肝纤维化方面具有功能。然而，在培养中扩增EPCs既复杂又昂贵。此前，我们建立了一种简单的方法，即通过将骨髓细胞以高密度点样简单接种来富集和扩增EPCs。本研究的目的是评估大鼠骨髓细胞高密度（HD）培养所获得的细胞能否在四氯化碳（CCl4）诱导的慢性肝损伤大鼠模型中预防肝纤维化。流式细胞术分析显示，HD培养的细胞富含EPCs，表达高水平的EPC标志物。与接受常规密度培养细胞治疗的动物相比，在CCl4诱导的肝损伤大鼠中脾内注射HD培养的骨髓细胞显示出增强的抗纤维化作用。移植后4周通过生化和组织学分析证实了抗纤维化作用。此外，HD培养的细胞可能通过增加新血管形成、刺激肝细胞增殖和抑制促纤维化因子表达发挥作用。HD培养是一种简单且经济有效的方法，有可能用于扩增骨髓细胞以治疗肝纤维化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f12/4177810/ae06adc34728/pone.0103603.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f12/4177810/87e7488c8fc7/pone.0103603.g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f12/4177810/7ee65adc134e/pone.0103603.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f12/4177810/b32c807edff4/pone.0103603.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f12/4177810/c70fbf9a04b1/pone.0103603.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f12/4177810/ae06adc34728/pone.0103603.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f12/4177810/87e7488c8fc7/pone.0103603.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f12/4177810/b54afab6aa55/pone.0103603.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f12/4177810/da184d045639/pone.0103603.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f12/4177810/7ee65adc134e/pone.0103603.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f12/4177810/b32c807edff4/pone.0103603.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f12/4177810/c70fbf9a04b1/pone.0103603.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f12/4177810/ae06adc34728/pone.0103603.g007.jpg

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