ABSTRACT
INTRODUCTION: Bone marrow-derived cells (BMCs) include stem cells capable of self-renewal and differentiation into a variety of cell types. Administration of granulocyte colony-stimulating factor (G-CSF) induces the circulation of BMCs in the peripheral blood. A phase II prospective trial was carried out for evaluation of BMC mobilization induced by multiple courses of G-CSF in cirrhotic patients. PATIENTS AND METHODS: Fifteen patients with advanced liver cirrhosis (Child-Pugh score ≥6 points) were enrolled and treated with a 3-day G-CSF course, administered at 3-month intervals for a total of four courses. BMC mobilization was assessed by evaluating CD34+ve cells using flow cytometry. Expressions of multiple hepatic and stem markers were assessed on mobilized CD34+ve cells. Feasibility and safety were explored; clinical and adverse events were compared to those of a control group. Telomere length was monitored to rule out early cell aging caused by G-CSF. RESULTS: A significant increase in G-CSF-induced circulating CD34+ve cells was consistently observed, although a progressive reduction of peak values was documented from cycle I to IV (p < 0.005). Mobilized CD34+ve cells expressed both stem and multiple hepatocyte markers, including mRNA of albumin and CYP2B6 (cytochrome P2 B6). Treatment was well tolerated, with no severe adverse events and no significant telomere length shortening following G-CSF. The procedure was safe. Overall, ten patients had either improved or had stable liver function tests (such as the Child-Pugh score), whereas five worsened and died from liver-related causes. CONCLUSION: This study demonstrates that G-CSF can be safely administrated up to four times over a 1-year period in decompensated cirrhotic patients. The repeated BMC mobilization favors the circulation of stem cells coexpressing hepatic markers and mRNA of liver-related genes.
ABSTRACT
Granulocyte colony-stimulating factor (G-CSF) induces a transient mobilization of hematopoietic progenitor cells from bone marrow to peripheral blood. Our aim was to evaluate safety of repeated courses of G-CSF in patients with amyotrophic lateral sclerosis (ALS), assessing disease progression and changes in chemokine and cytokine levels in serum and cerebrospinal fluid (CSF). Twenty-four ALS patients entered an open-label, multicenter trial in which four courses of G-CSF and mannitol were administered at 3-month intervals. Levels of G-CSF were increased after treatment in the serum and CSF. Few and transitory adverse events were observed. No significant reduction of the mean monthly decrease in ALSFRS-R score and forced vital capacity was observed. A significant reduction in CSF levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-17 (IL-17) was observed. G-CSF treatment was safe and feasible in a multicenter series of ALS patients. A decrease in the CSF levels of proinflammatory cytokines MCP-1 and IL-17 was found, indicating a G-CSF-induced central anti-inflammatory response.
