Therapeutic Use of Human Amnion-Derived Products: Cell-Based Therapy for Liver Disease
Abstract Purpose of Review Since the early 20th century, the placenta has started to regain its status as tissue with great potential in regenerative medicine. In particular, cells isolated from the fetal membrane, amnion epithelial cells (AEC), have been described for their proficient capacity to support regeneration at several organs, primarily the liver. Recent Findings The investigation on regenerative and corrective potential of human AEC has been conducted on relevant preclinical mo...
Source: Current Pathobiology Reports - July 12, 2016 Category: Laboratory Medicine Source Type: research

Involvement of Tight Junction Plaque Proteins in Cancer
Abstract Purpose of Review Here we review the molecular organization and protein–protein interactions of the following plaque proteins of tight junction (TJ): MAGI-1, -2 and -3, the polarity complex Par3/Par6/aPKC, afadin, MUPP1, PATJ, Pals1, cingulin, paracingulin, and JEAP. We analyze the status of these proteins in cancer tissue and their association to tumor suppressor proteins, kinases, and viral oncoproteins. Zonula occludens plaque proteins of the TJ are discussed separately in the preceding review within this issue. ...
Source: Current Pathobiology Reports - July 3, 2016 Category: Laboratory Medicine Source Type: research

Toward Organs on Demand: Breakthroughs and Challenges in Models of Organogenesis
Abstract Purpose of Review Irreversible organ failure remains a worldwide concern as demand for transplantable organs far outpaces the available supply. Apart from the demand for replacement organs to use to treat irreversible organ failure in civilian, there is a need of tissues or organs for wounded soldiers returning from battle. This review will discuss traditional three-dimensional (3D) cell culture techniques as well as newly developed technology platforms for the generation of transplantable tissues and organs on demand. ...
Source: Current Pathobiology Reports - July 1, 2016 Category: Laboratory Medicine Source Type: research

Zonula Occludens Proteins in Cancer
Abstract Purpose of Review In this review we describe the main characteristics of zonula occludens (ZO) proteins -1, -2 and -3, illustrate their interactions with multiple binding partners, analyze their evolution and their status in cancer tissue and their potential role as therapeutic cancer targets and predictors of patient outcome. Recent Findings Besides being present at the tight junction (TJ) cytoplasmic plaque, ZO proteins sequester transcription factors away from the nucleus, or ...
Source: Current Pathobiology Reports - July 1, 2016 Category: Laboratory Medicine Source Type: research

Tight Junctions and the Tumor Microenvironment
Abstract Purpose of review Tight junctions (TJs) are specialized differentiations of epithelial and endothelial cell membranes. TJs play an important role in the adhesion of cells and their interaction with each other. Most cancers originate from epithelial cells. Thus, it is of significance to examine the role of TJs in the tumor microenvironment (TME) and how they affect cancer metastasis. Recent findings In epithelium-derived cancers, intactness of the primary tumor mass is influenced ...
Source: Current Pathobiology Reports - June 30, 2016 Category: Laboratory Medicine Source Type: research

Whole-Organ Tissue Engineering: No Longer Just a Dream
Abstract Purpose of Review The true potential of the field of transplant surgery remains limited due to shortages of available transplantable allografts and, following transplantation, acute and chronic rejection with need for lifelong immune suppression. An alternative approach is to bioengineer organs to be utilized in vivo, replacing diseased or malfunctioning human organs. This revolutionary step in medicine could have virtually unlimited therapeutic potential. Recent Findings Multipl...
Source: Current Pathobiology Reports - June 28, 2016 Category: Laboratory Medicine Source Type: research

Apical –Basal Polarity as a Sensor for Epithelial Homeostasis: A Matter of Life and Death
< h3 class= " a-plus-plus " > Abstract < /h3 > < span class= " a-plus-plus abstract-section id-a-sec1 " > < h3 class= " a-plus-plus " > Purpose of Review < /h3 > < p class= " a-plus-plus " > Epithelial cells line tissues and serve an important functional role in maintaining a barrier between tissue compartments and protection from the external environment. Tight Junctions and apical –basal polarity function to establish and maintain epithelial structures to prevent leakage between cells and define distinct subcellular domains to localize signaling pathways within cells that control growth, survival, and migration. Disrup...
Source: Current Pathobiology Reports - June 26, 2016 Category: Laboratory Medicine Source Type: research

Apical–Basal Polarity as a Sensor for Epithelial Homeostasis: A Matter of Life and Death
Abstract Purpose of Review Epithelial cells line tissues and serve an important functional role in maintaining a barrier between tissue compartments and protection from the external environment. Tight Junctions and apical–basal polarity function to establish and maintain epithelial structures to prevent leakage between cells and define distinct subcellular domains to localize signaling pathways within cells that control growth, survival, and migration. Disruption of tight junctions and cell polarity is frequently observed in cancer. ...
Source: Current Pathobiology Reports - June 26, 2016 Category: Laboratory Medicine Source Type: research

The Contribution of Ig-Superfamily and MARVEL D Tight Junction Proteins to Cancer Pathobiology
Abstract The epithelial linings of eukaryotic organs form dynamically-regulated selectively-permeable barriers that control the movement of substances into (and out of) mucosal tissues. The principal structural determinants of epithelial barrier function are intercellular tight junctions (TJs), multi-protein complexes composed of claudin and non-claudin transmembrane proteins in addition to cytosolic linker proteins. As well as their crucial roles in barrier function, it is now well recognized that TJ proteins coordinate a variety of signaling and trafficking functions regulating physiological events such...
Source: Current Pathobiology Reports - May 19, 2016 Category: Laboratory Medicine Source Type: research

Liver Fibrosis and Leptin
Abstract Chronic liver damage can lead to hepatic fibrosis, a complex process caused by accumulation of extracellular matrix in the liver. Hepatic fibrosis is the final common pathway that may result in cirrhosis, and can ultimately require liver transplantation. The presence of obesity or overweight and the metabolic syndrome is a significant risk factor in the progression of this condition. In this paper, we discuss experimental and clinical evidence indicating the involvement of leptin, a major adipokine secreted by adipose tissue, in the modulation of fibrogenic process. In general, leptin has profibr...
Source: Current Pathobiology Reports - April 22, 2016 Category: Laboratory Medicine Source Type: research

How to Grow a Lung: Applying Principles of Developmental Biology to Generate Lung Lineages from Human Pluripotent Stem Cells
Abstract The number and severity of diseases affecting human lung development and adult respiratory function has stimulated great interest in new in vitro models to study the human lung. This review summarizes the most recent breakthroughs deriving lung lineages in a dish by directing the differentiation of human pluripotent stem cells. A variety of culturing platforms have been developed, including two-dimensional and three-dimensional (organoid) culture platforms, to derive specific cell types and structures of the lung. These stem cell-derived lung models will further our understanding of human lung de...
Source: Current Pathobiology Reports - April 17, 2016 Category: Laboratory Medicine Source Type: research

Generating Mini-Organs in Culture
Abstract The discovery of human-induced pluripotent stem cells (iPSCs) has provided new opportunities for studying human diseases and, ultimately, generating therapies. However, the practical application of iPSCs remains a challenge due to the failure of current two-dimensional culture methods targeted on generating single pure lineage cells. The developmental process of directed differentiation requires three-dimensional and temporal cellular interactions between multiple supporting cells and their environments. Recently, novel spatiotemporal stem cell culture methods for recapitulating organogenesis hav...
Source: Current Pathobiology Reports - April 10, 2016 Category: Laboratory Medicine Source Type: research

The Role of IL-17 Signaling in Regulation of the Liver –Brain Axis and Intestinal Permeability in Alcoholic Liver Disease
< h3 class= " a-plus-plus " > Abstract < /h3 > < p class= " a-plus-plus " > Alcoholic liver disease (ALD) progresses from a normal liver, to steatosis, steatohepatitis, fibrosis, and hepatocellular carcinoma (HCC). Despite intensive studies, the pathogenesis of ALD is poorly understood, in part due to a lack of suitable animal models which mimic the stages of ALD progression. Furthermore, the role of IL-17 in ALD has not been evaluated. We and others have recently demonstrated that IL-17 signaling plays a critical role in the development of liver fibrosis and cancer. Here we summarize the most recent evidence supporting th...
Source: Current Pathobiology Reports - February 29, 2016 Category: Laboratory Medicine Source Type: research

Fibroblast —Extracellular Matrix Interactions in Tissue Fibrosis
< h3 class= " a-plus-plus " > Abstract < /h3 > < p class= " a-plus-plus " > Activated myofibroblasts are key effector cells in tissue fibrosis. Emerging evidence suggests that myofibroblasts infiltrating fibrotic tissues originate predominantly from local mesenchyme-derived populations. Alterations in the extracellular matrix network play an important role in modulating fibroblast phenotype and function. In a pro-inflammatory environment, generation of matrix fragments may induce a matrix-degrading fibroblast phenotype. Deposition of ED-A fibronectin plays an important role in myofibroblast transdifferentiation. In ...
Source: Current Pathobiology Reports - February 29, 2016 Category: Laboratory Medicine Source Type: research

The Role of IL-17 Signaling in Regulation of the Liver–Brain Axis and Intestinal Permeability in Alcoholic Liver Disease
Abstract Alcoholic liver disease (ALD) progresses from a normal liver, to steatosis, steatohepatitis, fibrosis, and hepatocellular carcinoma (HCC). Despite intensive studies, the pathogenesis of ALD is poorly understood, in part due to a lack of suitable animal models which mimic the stages of ALD progression. Furthermore, the role of IL-17 in ALD has not been evaluated. We and others have recently demonstrated that IL-17 signaling plays a critical role in the development of liver fibrosis and cancer. Here we summarize the most recent evidence supporting the role of IL-17 in ALD. As a result of a collabor...
Source: Current Pathobiology Reports - February 19, 2016 Category: Laboratory Medicine Source Type: research