Feasibility and safety of G-CSF administration to induce bone marrow-derived cells mobilization in patients with end stage liver disease

Gaia, Silvia; Smedile, Antonina; Omedè, Paola; Olivero, Antonella; Sanavio, Fiorella; Balzola, F.; Ottobrelli, A.; Abate, Maria Lorena; Marzano, Alfredo; Rizzetto, M.; Tarella, Corrado

doi:10.1016/j.jhep.2006.02.018

Cited by 150 publications

(104 citation statements)

References 39 publications

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“…Our findings therefore highlight a therapeutic means by which these host DRs can be directly stimulated and we propose this pathway as a possible mechanism by which autologous BMC therapy may be beneficial in human liver disease. Animal models of BMC therapy for liver disease and clinical autologous BMC therapy studies are underway with encouraging preliminary results (2,(28)(29)(30). A recent report by our group has shown that a single portal vein injection of macrophages significantly reduces fibrosis in a model of chronic liver injury.…”

Section: Discussionmentioning

confidence: 99%

Bone marrow injection stimulates hepatic ductular reactions in the absence of injury via macrophage-mediated TWEAK signaling

Bird

Boulter

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

145

146

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Tissue progenitor cells are an attractive target for regenerative therapy. In various organs, bone marrow cell (BMC) therapy has shown promising preliminary results, but to date no definite mechanism has been demonstrated to account for the observed benefit in organ regeneration. Tissue injury and regeneration is invariably accompanied by macrophage infiltration, but their influence upon the progenitor cells is incompletely understood, and direct signaling pathways may be obscured by the multiple roles of macrophages during organ injury. We therefore examined a model without injury; a single i.v. injection of unfractionated BMCs in healthy mice. This induced ductular reactions (DRs) in healthy mice. We demonstrate that macrophages within the unfractionated BMCs are responsible for the production of DRs, engrafting in the recipient liver and localizing to the DRs. Engrafted macrophages produce the cytokine TWEAK (TNF-like weak inducer of apoptosis) in situ. We go on to show that recombinant TWEAK activates DRs and that BMC mediated DRs are TWEAK dependent. DRs are accompanied by liver growth, occur in the absence of liver tissue injury and hepatic progenitor cells can be isolated from the livers of mice with DRs. Overall these results reveal a hitherto undescribed mechanism linking macrophage infiltration to DRs in the liver and highlight a rationale for macrophage derived cell therapy in regenerative medicine.liver regeneration | adult stem cell

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Section: Discussionmentioning

confidence: 99%

Bone marrow injection stimulates hepatic ductular reactions in the absence of injury via macrophage-mediated TWEAK signaling

Bird

Boulter

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

145

146

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show abstract

“…18 Finally, G-CSF administration was able to induce BMC mobilization in cirrhotic patients, and a clinical improvement was registered in about 50% of treated individuals. 25 However, it remains unclear if G-CSF acts mainly by recruiting BMCs, or if it acts locally to facilitate the endogenous hepatic restoration program. Indeed, in the previously cited studies, G-CSF administration significantly accelerated the regeneration processes.…”

Section: Discussionmentioning

confidence: 99%

Granulocyte–Colony Stimulating Factor Promotes Liver Repair and Induces Oval Cell Migration and Proliferation in Rats

et al. 2007

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Background & Aims-Hepatic regeneration is a heterogeneous phenomenon involving several cell populations. Oval cells are considered liver stem cells, a portion of which derive from bone marrow (BM). Recent studies have shown that granulocyte-colony stimulating factor (G-CSF) may be effective in facilitating liver repair. However, it remains unclear if G-CSF acts by mobilizing BM cells, or if it acts locally within the liver microenvironment to facilitate the endogenous restoration program. In the present study, we assessed the involvement of G-CSF during oval cell activation.

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“…In a clinical trial, 8 patients affected by severe liver cirrhosis were administered G-CSF and the treatment was well tolerated in all the patients during a follow-up of 8 months, and mobilization of bone marrow stem cells co-expressing epithelial and stem markers was noted [15,16] . Two independent studies on a group of 24 patients and 18 patients [17,18] with severe liver cirrhosis resulted in a dose-dependent mobilization of good CD34+/CD133+ bone marrow stem cells and proved that the procedure was safe, but did not achieve any significant clinical improvement.…”

Section: In Situ Mobilization Of Bone Marrow Cells To the Livermentioning

confidence: 99%

Cell Based Therapy for Chronic Liver Disease: Role of Fetal Liver Cells in Restoration of the Liver Cell Functions

Tripura¹,

Khan²,

Pande³

2012

Liver Regeneration

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Feasibility and safety of G-CSF administration to induce bone marrow-derived cells mobilization in patients with end stage liver disease

Cited by 150 publications

References 39 publications

Bone marrow injection stimulates hepatic ductular reactions in the absence of injury via macrophage-mediated TWEAK signaling

Bone marrow injection stimulates hepatic ductular reactions in the absence of injury via macrophage-mediated TWEAK signaling

Granulocyte–Colony Stimulating Factor Promotes Liver Repair and Induces Oval Cell Migration and Proliferation in Rats

Cell Based Therapy for Chronic Liver Disease: Role of Fetal Liver Cells in Restoration of the Liver Cell Functions

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