粒细胞集落刺激因子（G-CSF）预处理的造血干细胞或G-CSF本身可加速肝损伤后的恢复并提高生存率，主要是通过促进内源性修复程序来实现。

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.

作者信息

Yannaki Evangelia, Athanasiou Evangelia, Xagorari Angeliki, Constantinou Varnavas, Batsis Ioannis, Kaloyannidis Panagiotis, Proya Evangelia, Anagnostopoulos Achilles, Fassas Athanasios

机构信息

Gene and Cell Therapy Center, Hematology Department/BMT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece.

出版信息

Exp Hematol. 2005 Jan;33(1):108-19. doi: 10.1016/j.exphem.2004.09.005.

DOI:10.1016/j.exphem.2004.09.005

PMID:15661404

Abstract

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 CCl4 in C57Bl6 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 CCl4 +/- 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 CCl4 group. Quantitative analysis showed higher percentage of BM-origin hepatocytes in the CCl4+G-CSF group compared with the CCl4 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.

摘要

目的

鉴于最近认识到骨髓（BM）细胞具有分化为肝细胞的潜力，我们研究了粒细胞集落刺激因子（G-CSF）动员的BM细胞归巢至受损肝脏并促进组织修复的可能性。我们还研究了损伤后肝脏细胞重建（内源性或BM来源）的起源。

方法

通过向C57Bl6小鼠注射四氯化碳建立急性和慢性肝损伤模型，并给予造血干细胞（HSC）动员剂量的G-CSF。将性别不匹配的BM移植到接受致死性照射的受体中，并给予四氯化碳+/-G-CSF治疗，通过免疫组织化学在肝切片中检测性别决定区Y染色体（sry）蛋白。采用sry和ki-67蛋白双重免疫组织化学法确定损伤后肝脏细胞重建的增殖细胞起源。

结果

在急性和慢性肝损伤模型中，给予G-CSF均能改善组织学损伤并加速再生过程。这伴随着G-CSF治疗组相对于四氯化碳组有显著的生存获益。定量分析显示，与四氯化碳组相比，四氯化碳+G-CSF组中BM来源的肝细胞百分比更高，尽管肝脏植入率仍然相当低。ki-67和sry双重染色表明，化学损伤和G-CSF治疗后的恢复加速主要是由宿主肝细胞（ki-67(+)/sry(-)）增殖增加介导的，而BM来源的细胞（ki-67(+)/sry(+)）的支持较少。