This study indicates that fibrin glue increases cell transplant survival, decreases infarct size, and increases blood flow to ischemic myocardium. Therefore, fibrin glue may have potential as a biomaterial scaffold to improve cellular cardiomyoplasty treat and MIs.

This largest single institution experience with OLT for HCC demonstrates prolonged survival after liver transplantation for tumors beyond Milan criteria but within UCSF criteria, both when classified by preoperative imaging and by explant pathology. Measured expansion of OLT criteria is justified for tumors not exceeding the UCSF criteria.

Therapeutic, III.

We have documented the key role of toll-like receptor 4 (TLR4) activation and its signaling pathway mediated by interferon (IFN) regulatory factor 3, in the induction of inflammation leading to the hepatocellular damage during liver ischemia/reperfusion injury (IRI). Because type I IFN is the major downstream activation product of that pathway, we studied its role in comparison with IFN-␥. Groups of type I (IFNAR), type II (IFNGR) IFN receptordeficient mice, along with wild-type (WT) controls were subjected to partial liver warm ischemia (90 minutes) followed by reperfusion (1-6 hours). Interestingly, IFNAR knockout (KO) but not IFNGR KO mice were protected from IR-induced liver damage, as evidenced by decreased serum alanine aminotransferase and preservation of tissue architecture. IRtriggered intrahepatic pro-inflammatory response, assessed by tumor necrosis factor (TNF-␣), interleukin 6 (IL-6), and chemokine (C-X-C motif) ligand 10 (CXCL-10) expression, was diminished selectively in IFNAR KO mice. Consistent with these findings, our in vitro cell culture studies have shown that: (1) although hepatocytes alone failed to respond to lipopolysaccharide (LPS), when co-cultured with macrophages they did respond to LPS via macrophage-derived IFN-␤; (2) macrophages required type I IFN to sustain CXCL10 production in response to LPS. This study documents that type I, but not type II, IFN pathway is required for IR-triggered liver inflammation/damage. Type I IFN mediates potential synergy between nonparenchyma and parenchyma cells in response to TLR4 activation. (HEPATOLOGY 2008;47:199-206.) L iver ischemia/reperfusion injury (IRI) occurs in multiple clinical settings including surgical interventions, trauma, and transplantation. 1-3 The mechanisms underlying liver IRI are complex but are known to involve interactions between both nonparenchyma cells, such as Kupffer cells (KC), and parenchyma cells, such as hepatocytes. Local leukocyte sequestration and activation (neutrophils, macrophages, and T cells) leads to the formation of reactive oxygen species, secretion of pro-inflammatory cytokines/chemokines, complement activation, and vascular cell adhesion molecule activation. Because IRI develops in the absence of exogenous antigens, it has been considered as an innate immune-mediated pro-inflammatory response.It was demonstrated that the mammalian sentinel tolllike-receptor (TLR) system plays a critical role in the development of IRI. 4-7 Indeed, TLR4 activation proved essential in the induction of inflammation in a warm liver IRI mouse model. In the absence of TLR4 but not TLR2 signaling, livers were protected from IRI, and intrahepatic induction of tumor necrosis factor (TNF-␣) and interleukin 1 (IL-1␤) was abolished. 7 It was also shown, by using bone marrow chimeras, that TLR4 expression on hematopoietic rather than parenchyma cells was instrumental in promoting liver IR-mediated damage. 8 TLR4 activation triggers 2 distinct signaling pathways leading to the induction of different immune-related genes. The MyD88...