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
Department of Internal Medicine, Cardioangiology and Hepatology, University of Bologna, Bologna, Italy.
Aliment Pharmacol Ther. 2008 May;27(10):932-9. doi: 10.1111/j.1365-2036.2008.03670.x. Epub 2008 Feb 29.
Bone marrow-derived stem cells (BMSC) and granulocyte colony-stimulating factor (G-CSF) have been proved to contribute to tissue regeneration after liver injury.
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.
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.
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.
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.
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。
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。
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。
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。
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。