Abstract
Bone marrow cells (BMC) migrate to the injured liver after transplantation, contributing to regeneration through multiple pathways, but mechanisms involved are unclear. This work aimed to study BMC migration, characterize cytokine profile, cell populations and proliferation in mice with liver fibrosis transplanted with GFP+ BMC. Confocal microscopy analysis showed GFP+ BMC near regions expressing HGF and SDF-1 in the fibrotic liver. Impaired liver cell proliferation in fibrotic groups was restored after BMC transplantation. Regarding total cell populations, there was a significant reduction in CD68+ cells and increased Ly6G+ cells in transplanted fibrotic group. BMC contributed to the total populations of CD144, CD11b and Ly6G cells in the fibrotic liver, related to an increment of anti-fibrotic cytokines (IL-10, IL-13, IFN-γ and HGF) and reduction of pro-inflammatory cytokines (IL-17A and IL-6). Therefore, HGF and SDF-1 may represent important chemoattractants for transplanted BMC in the injured liver, where these cells can give rise to populations of extrahepatic macrophages, neutrophils and endothelial progenitor cells that can interact synergistically with other liver cells towards the modulation of an anti-fibrotic cytokine profile promoting the onset of liver regeneration.
Highlights
Liver fibrosis is characterized by parenchymal chronic injury followed by extracellular matrix (ECM) accumulation
After GFP+ bone marrow cells (BMC) transplantation, the livers presented preserved parenchyma compared to fibrotic groups and significantly less collagen confirmed by quantification using the software Image Pro Plus 3.0 (Fig 1B and S1 Table)
After GFP+ BMC transplantation, the levels of glutamic-oxaloacetic transaminase (GOT) had a significant reduction compared to fibrotic groups
Summary
Liver fibrosis is characterized by parenchymal chronic injury followed by extracellular matrix (ECM) accumulation. Cirrhosis is the most advanced stage of liver fibrosis, leading to hepatic failure and with high rates of morbidity and mortality worldwide. Liver transplantation is the only effective therapy for cirrhosis currently, and insufficient compatible donors prompt the search for new therapies [1,2,3]. Evidence show that bone marrow cells (BMC) can restore liver function in chronic lesions, acting in a paracrine manner.
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