Endothelial Progenitor Cell Transplantation Improves the Survival Following Liver Injury in Mice

Induction of LYVE-1/stabilin-2-positive liver sinusoidal endothelial-like cells from embryoid bodies by modulation of adrenomedullin-RAMP2 signaling

“…In our study, LYVE-1-positive endothelial cells in EBs treated with AM and SB431542 expressed stabilin-2, and some exhibited fenestrae-like structures. In addition, transcription of the LSEC markers F8, Consistent with that idea, it was recently shown that transplanted sinusoidal endothelial cells can repopulate the liver endothelium and correct the phenotype of hemophilia A mice [7,15], and several reports have shown that endothelial progenitor cell transplantation ameliorates acute liver injury and liver cirrhosis in rats [18,23,31,32] . 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 23 Our second major finding is that AM-RAMP2 system is the potentital target for the induction of LSECs.…”

Cells as vehicles for therapeutic genes to treat liver diseases

“…They demonstrated that EPC generated high levels of hepatocyte growth factor, VEGF and heparin-binding EGF-like growth factor and stimulated the endogenous production of VEGF. 47 The same group reported in 2007 that EPC (characterized by the expression of CD133, VEGFR2, Tie-2 and CD31) given intravenously were able to reduce significantly liver damage and fibrogenesis in a model of liver cirrhosis induced by chronic administration of carbon tetrachloride. 48 In our group, 49 we observed that intrasplenic injection of EPC resulted in marked improvement and long-term survival of mice injected with an adenovirus encoding CD40L, a model of fulminant hepatitis with 100% mortality.…”

“…44, 45 Suh and co-workers reported that human EPC obtained by Cells as vehicles for therapeutic genes J Prieto et al culturing in specific medium peripheral blood mononuclear cells and given to nude mice induced an acceleration of wound healing by local production of growth factors, stimulation of tissue repair and neovascularization. 46 In 2006, Taniguchi et al 47 showed that EPC obtained from human peripheral blood mononuclear cells or from murine BM after culture in specific medium for 10 days and given intrasplenically were able to ameliorate acute carbon tetrachloride liver damage in nude mice (human EPC) or in BALB/c mice (murine EPC) and to improve survival. They demonstrated that EPC generated high levels of hepatocyte growth factor, VEGF and heparin-binding EGF-like growth factor and stimulated the endogenous production of VEGF.…”

Differential Roles of Angiogenesis in the Induction of Fibrogenesis and the Resolution of Fibrosis in Liver

“…44) EPC transplantation was shown to effectively promote the remodeling of tissues damaged by liver fibrosis in the dimethylnitrosamine (DMN) rat liver fibrosis model. 45,46) In a recent experimental study, VEGF played a dual and opposing role in liver fibrogenesis and fibrolysis through critical effects of VEGF on LSEC phenotype, sinusoidal permeability, monocyte infiltration, and scar-associated macrophage (SAM) function. Mechanistically, a VEGF-driven C-X-C motif chemokine 9 (CXCL9)-MMP13 axis was identified for mediating fibrosis resolution.…”