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肝硬化患者的干细胞动员与采集

Stem cell mobilization and collection in patients with liver cirrhosis.

作者信息

Lorenzini S, Isidori A, Catani L, Gramenzi A, Talarico S, Bonifazi F, Giudice V, Conte R, Baccarani M, Bernardi M, Forbes S J, Lemoli R M, Andreone P

机构信息

Department of Internal Medicine, Cardioangiology and Hepatology, University of Bologna, Bologna, Italy.

出版信息

Aliment Pharmacol Ther. 2008 May;27(10):932-9. doi: 10.1111/j.1365-2036.2008.03670.x. Epub 2008 Feb 29.

Abstract

BACKGROUND

Bone marrow-derived stem cells (BMSC) and granulocyte colony-stimulating factor (G-CSF) have been proved to contribute to tissue regeneration after liver injury.

AIMS

To test the safety of G-CSF and define the exact dose capable of mobilizing BMSC in the majority of patients with liver cirrhosis; and to assess the feasibility of leukapheresis to collect BMSC from peripheral blood.

METHODS

In this study, we treated 18 patients affected by liver cirrhosis with increasing doses of G-CSF to mobilize CD34(+) and CD133(+) BMSC into the peripheral blood.

RESULTS

The dose-finding phase demonstrated that 15 microg/kg/day of G-CSF is the optimal dose to mobilize both CD34(+) and CD133(+) stem cells. Circulating BMSC were collected by a single step leukapheresis in three patients and the mean number of CD34(+) and CD133(+) cells cryopreserved was 1.3 +/- 0.7 and 1.2 +/- 0.5 x 10(6)/kg, respectively. No severe adverse events were observed during the drug administration and stem cell collection. Noteworthy is, none of the patients showed a significant modification of liver function.

CONCLUSIONS

Our study demonstrates that G-CSF administration and BMSC collection from the peripheral blood is possible and safe in patients with liver cirrhosis. The optimal dose to mobilize BMSC in cirrhotics is 15 microg/kg/day. At this dose, G-CSF does not seem to modify the residual liver function in cirrhotic patients.

摘要

背景

骨髓来源的干细胞(BMSC)和粒细胞集落刺激因子(G-CSF)已被证明有助于肝损伤后的组织再生。

目的

测试G-CSF的安全性,并确定能够动员大多数肝硬化患者体内BMSC的确切剂量;评估通过白细胞分离术从外周血中采集BMSC的可行性。

方法

在本研究中,我们用递增剂量的G-CSF治疗了18例肝硬化患者,以将CD34(+)和CD133(+) BMSC动员到外周血中。

结果

剂量探索阶段表明,15μg/kg/天的G-CSF是动员CD34(+)和CD133(+)干细胞的最佳剂量。通过单步白细胞分离术从3例患者中采集了循环BMSC,冷冻保存的CD34(+)和CD133(+)细胞的平均数量分别为1.3±0.7和1.2±0.5×10(6)/kg。在药物给药和干细胞采集过程中未观察到严重不良事件。值得注意的是,所有患者的肝功能均未出现显著改变。

结论

我们的研究表明,在肝硬化患者中给予G-CSF并从外周血中采集BMSC是可行且安全的。动员肝硬化患者体内BMSC的最佳剂量为15μg/kg/天。在此剂量下,G-CSF似乎不会改变肝硬化患者的残余肝功能。

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