Stem cell mobilization and collection in patients with liver cirrhosis

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 μg/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 × 10⁶/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 μg/kg/day. At this dose, G-CSF does not seem to modify the residual liver function in cirrhotic patients.