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HGF 和 FGF4 预处理的间充质干细胞可减少小鼠肝纤维化。

Mesenchymal Stem Cells Pretreated with HGF and FGF4 Can Reduce Liver Fibrosis in Mice.

机构信息

National Centre of Excellence in Molecular Biology, 87 West Canal Bank Road, Thokar Niaz Baig, Lahore 53700, Pakistan ; Stem Cells Regenerative Medicine Lab, Department of Biochemistry, Abdul Wali Khan University, Mardan, Khyber Pakhtunkhwa 23200, Pakistan.

National Centre of Excellence in Molecular Biology, 87 West Canal Bank Road, Thokar Niaz Baig, Lahore 53700, Pakistan.

出版信息

Stem Cells Int. 2015;2015:747245. doi: 10.1155/2015/747245. Epub 2015 Jan 20.

DOI:10.1155/2015/747245
PMID:25685159
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4320872/
Abstract

Stem cells have opened a new avenue to treat liver fibrosis. We investigated in vitro and in vivo the effect of cytokine (HGF and FGF4) pretreated MSCs in reduction of CCl4 liver injury. Mouse MSCs were pretreated with cytokines to improve their ability to reduce CCl4 injury. In vitro we gave CCl4 injury to mouse hepatocytes and cocultured it with untreated and cytokines pretreated MSCs. For in vivo study we labeled MSCs with PKH-26 and transplanted them into CCl4 injured mice by direct injection into liver. In vitro data showed that cytokines pretreated MSCs significantly reduce LDH level and apoptotic markers in CCl4 injured hepatocytes cocultured model. Furthermore the cytokines pretreated MSCs also improved cell viability and enhanced hepatic and antiapoptotic markers in injured hepatocytes cocultured model as compared to untreated MSCs. In vivo data in cytokines pretreated group demonstrated greater homing of MSCs in liver, restored glycogen storage, and significant reduction in collagen, alkaline phosphatase, and bilirubin levels. TUNEL assay and real time PCR also supported our hypothesis. Therefore, cytokines pretreated MSCs were shown to have a better therapeutic potential on reduction of liver injury. These results demonstrated the potential utility of this novel idea of cytokines pretreated MSCs for the treatment of liver fibrosis.

摘要

干细胞为治疗肝纤维化开辟了新途径。我们研究了细胞因子（HGF 和 FGF4）预处理 MSC 减少 CCl4 肝损伤的体内外作用。用细胞因子预处理小鼠 MSC 以提高其减轻 CCl4 损伤的能力。在体外，我们给予 CCl4 损伤的小鼠肝细胞，并与未经处理和细胞因子预处理的 MSC 共培养。在体内研究中，我们用 PKH-26 标记 MSC，并通过直接注射到肝脏将其移植到 CCl4 损伤的小鼠中。体外数据表明，细胞因子预处理的 MSC 可显著降低 CCl4 损伤肝细胞共培养模型中的 LDH 水平和凋亡标志物。此外，与未经处理的 MSC 相比，细胞因子预处理的 MSC 还提高了细胞活力，并增强了损伤肝细胞共培养模型中的肝和抗凋亡标志物。细胞因子预处理组的体内数据表明，MSC 在肝脏中的归巢增加，糖原储存得到恢复，胶原、碱性磷酸酶和胆红素水平显著降低。TUNEL 检测和实时 PCR 也支持我们的假设。因此，细胞因子预处理的 MSC 显示出在减轻肝损伤方面具有更好的治疗潜力。这些结果证明了细胞因子预处理 MSC 治疗肝纤维化这一新颖想法的潜在应用价值。

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