G-CSF-primed hematopoietic stem cells or G-CSF per se accelerate recovery and improve survival after liver injury, predominantly by promoting endogenous repair programs
G-CSF-primed hematopoietic stem cells or G-CSF per se accelerate recovery and improve survival after liver injury, predominantly by promoting endogenous repair programs
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DOI：
10.1016/j.exphem.2004.09.005
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发表时间：
2005-01-01
影响因子：
2.6
通讯作者：
Fassas, A
中科院分区：
文献类型：
--
作者：
Yannaki, E;Athanasiou, E;Fassas, A
客观的。基于最近认识到的骨髓 (BM) 细胞产生肝细胞的潜力，我们研究了粒细胞集落刺激因子 (G-CSF) 动员的 BM 细胞可以归巢到受损肝脏并促进组织修复的可能性。我们还检查了损伤后重建肝脏的细胞（内源性或BM）的起源。方法。通过向 C57B16 小鼠注射 CC14 产生急性和慢性肝损伤模型，并以造血干细胞 (HSC) 动员剂量施用 G-CSF。将性别不匹配的骨髓移植到经致死性辐射的受者体内并用 CC14 +/- G-CSF 治疗后，通过免疫组织化学在肝脏切片中检测到 sry（Y 染色体性别决定区）蛋白。使用sry和ki-67蛋白的双重免疫组化来确定损伤后重建肝脏的增殖细胞的起源。结果。在急性和慢性肝损伤模型中，G-CSF 给药均改善了组织学损伤并加速了再生过程。与 CC14 组相比，G-CSF 治疗组具有显着的生存获益。定量分析显示，与CC14组相比，CC14+G-CSF组中BM来源的肝细胞百分比较高，但肝脏移植率仍然相当低。 ki-67和sry双重染色表明，化学损伤和G-CSF处理后的恢复加速主要是由宿主肝细胞增殖增加(ki-67(+)/sry(-))介导的，而BM来源细胞(ki-67(+)/sry(+))的支持较少。结论。 G-CSF 治疗显着改善了化学损伤小鼠的存活率和肝脏组织学，主要是通过促进内源性修复机制。因此，G-CSF动员可能为治疗人类急性和慢性肝病提供一种新的治疗方法。 (C) 2005 年国际实验血液学学会。由爱思唯尔公司出版
Objective. On the basis of the recently recognized potential of bone marrow (BM) cells to give rise to hepatocytes, we investigated the possibility that granulocyte colony-stimulating factor (G-CSF)-mobilized BM cells could home to the injured liver and promote tissue repair. We also examined the origin of cells (endogenous or BM) reconstituting liver after damage.Methods. Acute and chronic liver injury models were generated by injecting CC14 in C57B16 mice and G-CSF was administered in hematopoietic stem cell (HSC) mobilization doses. After sex-mismatched BM transplantation into lethally irradiated recipients and treatment with CC14 +/- G-CSF, sry (sex-determining region for Y chromosome) protein was detected by immunohistochemistry in liver sections. Double immunohistochemistry for sry and ki-67 protein was used to define the origin of proliferating cells reconstituting liver after injury.Results. In both acute and chronic liver injury model, G-CSF administration ameliorated the histological damage and accelerated the regeneration process. This was accompanied by a strong survival benefit in G-CSF-treated group vs CC14 group. Quantitative analysis showed higher percentage of BM-origin hepatocytes in the CC14 + G-CSF group compared with the CC14 group, although the liver engraftment rate still remained rather low. Double staining for ki-67 and sry demonstrated that the recovery acceleration after chemical injury and G-CSF treatment was mainly mediated by increased proliferation of host hepatocytes (ki-67(+)/sry(-)) with less support from BM-origin cells (ki-67(+)/sry(+)).Conclusion. G-CSF treatment significantly improved survival and liver histology in chemically injured mice, predominantly by promoting endogenous repair mechanisms. Therefore, mobilization with G-CSF might offer a novel therapeutic approach for the treatment of acute and chronic liver diseases in humans. (C) 2005 International Society for Experimental Hematology. Published by Elsevier Inc.