Silvia Gaia1, Antonella Olivero2, Antonina Smedile2, Marco Ruella3, Maria Lorena Abate2, Maurizio Fadda4, Emanuela Rolle2, Paola Omedè5, Paola Bondesan5, Roberto Passera6, Alessandra Risso7, Manuela Aragno8, Alfredo Marzano2, Alessia Ciancio2, Mario Rizzetto2, Corrado Tarella3. 1. Department of Gastro-hepatology, A.O. Città della Salute e della Scienza, S. Giovanni Battista Hospital, University of Turin, C. Bramante 88, 10126, Turin, Italy. silvia.gaia74@gmail.com. 2. Department of Gastro-hepatology, A.O. Città della Salute e della Scienza, S. Giovanni Battista Hospital, University of Turin, C. Bramante 88, 10126, Turin, Italy. 3. Division of Hematology and Cell Therapy, University of Torino, Mauriziano Hospital, Turin, Italy. 4. Department of Clinical Nutrition, A.O. Città della Salute e della Scienza, S. Giovanni Battista Hospital, University of Turin, C. Bramante 88, 10126, Turin, Italy. 5. Division of Hematology 1, A.O. Città della Salute e della Scienza, S. Giovanni Battista Hospital, University of Turin, C. Bramante 88, 10126, Turin, Italy. 6. Division of Nuclear Medicine 2, A.O. Città della Salute e della Scienza, S. Giovanni Battista Hospital, University of Turin, C. Bramante 88, 10126, Turin, Italy. 7. Molecular Biotechnology Center, University of Torino, Turin, Italy. 8. Department of Medicine and Experimental Oncology, University of Torino, Turin, Italy.
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.
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.
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Authors: Mamun Al Mahtab; Sheikh Mn Alam; Ahmed L Moben; Ruksana Raihan; Mohammad A Alam; Mohammad A Rahim; Mohammad H Uddin; Sheikh Mohammad Fazle Akbar Journal: Euroasian J Hepatogastroenterol Date: 2017-05-05