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

Prevention of liver fibrosis by intrasplenic injection of high-density cultured bone marrow cells in a rat chronic liver injury model.
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在大鼠慢性肝损伤模型中脾内注射高密度培养的骨髓细胞预防肝纤维化。

DOI:
10.1371/journal.pone.0103603
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Zhang WJ
Zhang WJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Lian J;Lu Y;Xu P;Ai A;Zhou G;Liu W;Cao Y;Zhang WJ

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骨髓内皮祖细胞 (EPC) 已被证明可有效预防慢性肝损伤中的肝纤维化。然而,EPC 在文化中的扩展是复杂且广泛的。此前,我们已经建立了一种简单的方法,可以通过在高密度点中简单接种骨髓细胞来富集和扩增 EPC。本研究的目的是评估大鼠骨髓细胞高密度 (HD) 培养物是否可以预防四氯化碳 (CCl4) 诱导的慢性肝损伤大鼠模型的肝纤维化。流式细胞术分析表明,HD 培养的细胞富含 EPC,表达高水平的 EPC 标记。与用常规密度培养的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形成作用。移植后4周的生化和组织学分析证明了抗纤维化作用。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来发挥作用。 HD 培养是一种简单且具有成本效益的程序,有可能用于扩增骨髓细胞以治疗肝纤维化。
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.
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