The injected cells functioned mainly through a paracrine mechanism

Obviously, the secretion of growth factors played a crucial role in the antifibrogenic process, which is consistent with other reports. Interestingly, differentiation of transplanted cells into hepatocytes was not observed, indicating that the NPS-1034 injected cells functioned mainly through a paracrine mechanism to prevent liver fibrosis and regeneration, rather than by direct differentiation into hepatocytes. The enhanced antifibrogenic effect of HD cultured bone marrow cells could also be explained by the natural liver repairing mechanism after injury. It is known that in many tissues, the response to injury involves angiogenesis, which Trimebutine requires a supply of growth factors, nutrients, and oxygen. In liver regeneration, resident sinusoidal endothelial cells, have been shown to proliferate, migrate, and reconstruct hepatic sinusoids. As reviewed recently, following CCl4-induced injury, endothelial cells of the liver portal vein contract with lumen constriction, and liver tissue becomes ischemic and hypoxic. Infusion of EPCs or VEGF can enhance neovascularization, relieving portal pressure and eventually ameliorating the fibrosis. In the present research, HD culture of bone marrow cells enriched EPCs more than RD culture. In addition, IHC of frozen sections confirmed that more blood vessels were formed in the liver after treatment with HD cultured cells. The enhancement of capillary density was coinciding with the treatment by EPCs Prevention of liver fibrosis and liver reconstitution of DMNtreated rat liver by transplanted EPCs. Interestingly, these findings are conflicting with the reports that liver fibrogenesis and angiogenesis develop in parallel during progression towards cirrhosis. It has been reported that the drugs that specifically inhibit angiogenesis could reduce hepatic fibrosis. However, other studies showed that an inhibition of angiogenesis could even worsen fibrosis. Theoretically, angiogenesis is important for the tissue repair. Therefore, in this study, the enhanced blood supply could prevent injury, stimulate regeneration, and inhibit fibrosis.

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