Retinal endothelial cells line the arborizing microvasculature that supplies and drains the neural retina. The anatomical and physiological characteristics of these endothelial cells are consistent with nutritional requirements and protection of a tissue critical to vision. On the one hand, the endothelium must ensure the supply of oxygen and other nutrients to the metabolically active retina, and allow access to circulating cells that maintain the vasculature or survey the retina for the presence of potential pathogens. On the other hand, the endothelium contributes to the blood-retinal barrier that protects the retina by excluding circulating molecular toxins, microorganisms, and pro-inflammatory leukocytes. Features required to fulfill these functions may also predispose to disease processes, such as retinal vascular leakage and neovascularization, and trafficking of microbes and inflammatory cells. Thus, the retinal endothelial cell is a key participant in retinal ischemic vasculopathies that include diabetic retinopathy and retinopathy of prematurity, and retinal inflammation or infection, as occurs in posterior uveitis. Using gene expression and proteomic profiling, it has been possible to explore the molecular phenotype of the human retinal endothelial cell and contribute to understanding of the pathogenesis of these diseases. In addition to providing support for the involvement of well-characterized endothelial molecules, profiling has the power to identify new players in retinal pathologies. Findings may have implications for the design of new biological therapies. Additional progress in this field is anticipated as other technologies, including epigenetic profiling methods, whole transcriptome shotgun sequencing, and metabolomics, are used to study the human retinal endothelial cell.

Retinal and choroidal vascular endothelial cells display distinctive gene expression profiles. The findings suggest the possibility of treating posterior uveitis by targeting specific interactions between the retinal endothelial cell and an infiltrating leukocyte.

FKN is expressed in various ocular tissues and cells. Inflammatory mediator modulation of ocular FKN expression suggests that this adhesive chemokine may play important roles in regulating leukocyte efflux in inflammatory eye diseases, such as anterior uveitis and retinochoroiditis.

The hepatitis B virus X protein (HBx) of the hepatitis B virus (HBV) has been involved in the development of hepatocellular carcinoma (HCC). However, its possible contribution to the metastatic spreading of liver tumors has not been explored so far. We report here the ability of HBx to enhance cell motility, both alone and in synergy with growth factors, and to induce a migratory phenotype in transformed cells. HBx altered the cellular morphology by inducing the formation of pseudopodial protrusions and cytoskeletal rearrangements, which was accompanied by the polarization of cell-surface adhesion molecules, including the hyaluronan (HA) receptor, CD44. The hepatitis B virus (HBV) is a hepatotropic virus composed of a partially double-stranded circular DNA genome that causes acute and chronic hepatic injury. Persistent HBV infection is strongly associated with the development of hepatocellular carcinoma (HCC). 1 Four genes, S/preS, C/preC, P, and X, are encoded by the viral genome. 2 The viral X gene encodes a 17-kd protein, termed HBx, that functions as a transcriptional activator of a variety of viral and cellular genes (reviewed in Yen 3 ). In addition, HBx plays important roles in the viral life cycle as shown in in vivo animal studies, 4-6 and in transfection-based replication assays. 7-9 Different animal models have provided evidence for a role of HBx in the generation of hepatic carcinomas. In transgenic mice, HBx was shown to either induce HCC or to potentiate c-myc and chemical carcinogen-induced liver cancer. 10-13 Moreover, immortalized hepatocytes stably transfected with the HBV genome form metastatic tumors upon inoculation in nude mice. 14 Different reports have described that HBx is expressed in HCCs, 15,16 and that HBx mRNA selectively accumulates in HCCs from hepatitis B surface antigen-negative patients, 15 suggesting a possible role for HBx in late events of the carcinoma development.A possible explanation for the pro-oncogenic potential of HBx has arisen from its ability to activate several signal transduction cascades and transcription factors. [17][18][19][20][21][22][23] In addition, HBx is capable of interacting with a wide variety of cellular proteins, including cell-cycle control and apoptosis proteins 24 and DNA repair molecules, 25,26 which may also contribute to cellular transformation. Previous studies have mainly focused on the involvement of signaling cascades in the activation of gene expression by HBx, but activation of these transduction pathways also may lead to profound cytologic changes. These could be quite important in explaining biological properties of tumor cells, such as acquisition of metastatic properties. In this regard, metastasis of HCC is frequently observed even at relatively early stages of the disease and appears to be the main cause of liver failure and death in HCC patients. 27,28 Tumor metastasis is a multistep process, requiring detachment of the cells from the primary tumor, migration of the tumor cells through the extracellular matrix, entry into the lym...

Large body surface area burns pose significant therapeutic challenges. Clinically, the extent and depth of burn injury may mandate the use of allograft for temporary wound coverage while autografts are serially harvested from the same donor areas. The paucity of donor sites in patients with burns involving large surface areas highlights the need for better skin substitutes that can achieve early and complete coverage and retain normal skin durability with minimal donor requirements. We have isolated autologous stem cells from the adipose layer of surgically debrided burned skin (dsASCs), using a point-of-care stem cell isolation device. These cells, in a collagen—polyethylene glycol fibrin-based bilayer hydrogel, differentiate into an epithelial layer, a vascularized dermal layer, and a hypodermal layer. All-trans-retinoic acid and fenofibrate were used to differentiate dsASCs into epithelial-like cells. Immunocytochemical analysis showed a matrix- and time-dependent change in the expression of stromal, vascular, and epithelial cell markers. These results indicate that stem cells isolated from debrided skin can be used as a single autologous cell source to develop a vascularized skin construct without culture expansion or addition of exogenous growth factors. This technique may provide an alternative approach for cutaneous coverage after extensive burn injuries.