EDA Fibronectin Microarchitecture and YAP Translocation During Wound Closure.

Fibronectin (Fn) is an extracellular matrix glycoprotein with mechanosensitive structure-function. EDA Fn, a Fn isoform, is not present in adult tissue but is required for tissue repair. Curiously, EDA Fn is linked to both regenerative and fibrotic tissue repair.

Delivery technologies for therapeutic targeting of fibronectin in autoimmunity and fibrosis applications.

Fibronectin (FN) is a critical component of the extracellular matrix (ECM) contributing to various physiological processes, including tissue repair and immune response regulation. FN regulates various cellular functions such as adhesion, proliferation, migration, differentiation, and cytokine release. Alterations in FN expression, deposition, and molecular structure can profoundly impact its interaction with other ECM proteins, growth factors, cells, and associated signaling pathways, thus influencing the progress of diseases such as fibrosis and autoimmune disorders.

Rift Valley fever virus induces fetal demise in Sprague-Dawley rats through direct placental infection.

Rift Valley fever virus (RVFV) infections in pregnant livestock cause high rates of fetal demise; miscarriage in pregnant women has also been associated with RVFV infection. To address how RVFV infection during pregnancy causes detrimental effects on the fetus, we developed a pregnant rodent model of RVFV infection. We found that pregnant rats were more susceptible to RVFV-induced death than their nonpregnant counterparts and that RVFV infection resulted in intrauterine fetal death and severe congenital abnormalities, even in pups from infected asymptomatic pregnant rats.

Successful Management of Giant Placental Chorangioma by Microcoil Embolization.

Optimal prenatal management of giant placental chorangioma (also known as chorioangioma, angiomyxoma, fibroangiomyxoma, or fibroma) has yet to be determined. Interventions intended to devascularize the tumor such as interstitial laser, bipolar coagulation, fetoscopic laser photocoagulation, and chemical embolization have met mixed results. We report a minimally invasive, extra-amniotic approach, technically similar to cordocentesis, of microcoil embolization of the feeding vessel.

Diploid/triploid mixoploidy: A consequence of asymmetric zygotic segregation of parental genomes.

Triploidy is the presence of an extra haploid set of chromosomes and can exist in complete or mosaic form. The extra haploid set of chromosomes in triploid cells can be of maternal or paternal origin. Diploid/triploid mixoploidy is a unique form of triploid mosaicism that requires the aberrant segregation of entire parental genomes into distinct blastomere lineages (heterogoneic cell division) at the earliest zygotic divisions.

Diagnostic Utility of Pax8, Pax2, and NGFR Immunohistochemical Expression in Pediatric Renal Tumors.

Pediatric renal tumors (PRT) with small round blue or spindle cell morphology can be diagnostically challenging and only a limited number of immunohistochemical markers have been documented to help in the diagnosis: paired box (Pax) 2 and nerve growth factor receptor (NGFR) positivity have been demonstrated in Wilms tumor (WT) and clear cell sarcoma of the kidney (CCSK), respectively. However, the immunohistochemical expression of these markers in other PRT remains unknown. This study investigated Pax8, Pax2, and NGFR immunophenotype in a large series of PRT.

Cystic pancreatic neoplasm in pregnancy: a case report and review of the literature.

Mucinous cystic neoplasms of the pancreas are rare tumors that tend to occur in young women. They are thought to be responsive to sex hormones. We report a case of a 32-year-old pregnant woman with a 7-month history of pain and a left upper quadrant abdominal mass.

Eccrine porocarcinoma: Report of a case with fine needle aspiration cytology, histopathology and immunohistochemistry.

Background: Although relatively rare, eccrine porocarcinoma (EP) is widely recognized in the literature as the most common of the sweat gland adenocarcinoma types. EP is an adenocarcinoma of the eccrine sweat gland with a propensity to recur locally and metastasize to regional lymph nodes. This paper presents the second case of fine needle aspiration (FNA) cytology of an EP along with histopathology and immunohistochemistry.

International neuroblastoma pathology classification adds independent prognostic information beyond the prognostic contribution of age.

Age has been used as a prognostic factor for patients with peripheral neuroblastic tumours (pNTs). The latest analysis disclosed a cut-off around 18 months for the optimal prognostic distinction. The International Neuroblastoma Pathology Classification (INPC) distinguishes favourable and unfavourable histology based on the age-appropriate evaluation of histologic indicators (grade of neuroblastic differentiation, mitosis-karyorrhexis index) in the categories of neuroblastoma and ganglioneuroblastoma, nodular.

Genetic approaches to craniofacial tissue repair.

This review discusses in some detail the opportunities and challenges of applying gene therapy to the important clinical problem of wound repair and regeneration.

Sustained effects of gene-activated matrices after CNS injury.

We show that when gene-activated matrices (GAM) are placed between the proximal and distal stumps of severed rat optic nerves, DNA is retained within the GAM, promoting sustained transgene expression in the optic nerve, in the GAM itself, and, more importantly, in axotomized retinal ganglion cells (RGC). Plasmids that encode basic fibroblast growth factor (FGF2), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT3) promote sustained survival of RGC for over 3 months after the initial injury. These findings suggest that immobilized DNA implanted into a CNS lesion will be delivered by axon terminal uptake and retrograde transport to axotomized neurons.

Tissue engineering via local gene delivery: update and future prospects for enhancing the technology.

This review describes the status of a local plasmid-based gene transfer technology known as the gene activated matrix (GAM). Studies over the past 6 years suggest that GAM may serve as a platform technology for local gene delivery in the wound bed of various tissues and organs. These studies demonstrated that plasmid encoding genes can be delivered to acutely injured tendon, ligament, bone, muscle, skin and nerve.

Tissue engineering via local gene delivery.

The first goal of this review is to describe a local plasmid gene transfer technology known as the gene activated matrix (GAM). GAM was the first gene therapy designed specifically for tissue engineering applications, and the mechanism of action of plasmid gene transfer is closely tied to the normal sequence of events associated with wound healing. The normal sequence of wound healing events is stereotyped for most tissues, and one assumption has been that GAM could serve as a platform technology for local gene delivery in various tissues and organs.

Options for tissue engineering to address challenges of the aging skeleton.

There will be more than 52 million Americans over the age of 65 by the year 2020 (U.S. Census Bureau).

Activin betaC and betaE genes are not essential for mouse liver growth, differentiation, and regeneration.

The liver is an essential organ that produces several serum proteins, stores vital nutrients, and detoxifies many carcinogenic and xenobiotic compounds. Various growth factors positively regulate liver growth, but only a few negative regulators are known. Among the latter are the transforming growth factor beta (TGF-beta) superfamily members TGF-beta1 and activin A.

Developmental expression of latent transforming growth factor beta binding protein 2 and its requirement early in mouse development.

Latent transforming growth factor beta (TGF-beta) binding protein 2 (LTBP-2) is an integral component of elastin-containing microfibrils. We studied the expression of LTBP-2 in the developing mouse and rat by in situ hybridization, using tropoelastin expression as a marker of tissues participating in elastic fiber formation. LTBP-2 colocalized with tropoelastin within the perichondrium, lung, dermis, large arterial vessels, epicardium, pericardium, and heart valves at various stages of rodent embryonic development.

Gene therapy for tissue repair and regeneration.

This review presents a current overview of the discipline of human gene therapy. In addition, a gene therapy method is described in which plasmid genes are transferred from a structural matrix carrier into fresh wound sites so as to enhance tissue repair and regeneration. The potential to develop a gene therapy for bone regeneration is discussed in detail.

A new in vivo microvascular preparation of the hamster ovary.

Ovarian function in the cycling female is intimately related to and dependent upon significant microvascular regulation and restructuring. To enable investigation of the microvascular determinants of ovarian function, we present an in vivo preparation of the golden hamster ovary. The preparation does not compromise the ovarian vascular supply.

Cyclic mechanical strain regulates the development of engineered smooth muscle tissue.

We show that the appropriate combinations of mechanical stimuli and polymeric scaffolds can enhance the mechanical properties of engineered tissues. The mechanical properties of tissues engineered from cells and polymer scaffolds are significantly lower than the native tissues they replace. We hypothesized that application of mechanical stimuli to engineered tissues would alter their mechanical properties.

Engineered smooth muscle tissues: regulating cell phenotype with the scaffold.

Culturing cells on three-dimensional, biodegradable scaffolds may create tissues suitable either for reconstructive surgery applications or as novel in vitro model systems. In this study, we have tested the hypothesis that the phenotype of smooth muscle cells (SMCs) in three-dimensional, engineered tissues is regulated by the chemistry of the scaffold material. Specifically, we have directly compared cell growth and patterns of extracellular matrix (ECM) (e.

Localized, direct plasmid gene delivery in vivo: prolonged therapy results in reproducible tissue regeneration.

The inability to deliver growth factors locally in a transient but sustained manner is a substantial barrier to tissue regeneration. Systems capable of localized plasmid gene delivery for prolonged times may offer lower toxicity and should be well-suited for growth factor therapeutics. We investigated the potency of plasmid gene delivery from genes physically entrapped in a polymer matrix (gene activated matrix) using bone regeneration as the endpoint in vivo.

DNA delivery from polymer matrices for tissue engineering.

We have proposed engineering tissues by the incorporation and sustained release of plasmids encoding tissue-inductive proteins from polymer matrices. Matrices of poly(lactide-co-glycolide) (PLG) were loaded with plasmid, which was subsequently released over a period ranging from days to a month in vitro. Sustained delivery of plasmid DNA from matrices led to the transfection of large numbers of cells.

Potential role for direct gene transfer in the enhancement of fracture healing.

This paper describes the use of localized transient gene therapy for the augmentation of fracture healing. It introduces a method involving the delivery of plasmid deoxyribonucleic acid via a three dimensional matrix into a wound, with in vivo transfection of wound repair cells resulting, their subsequent expression of factors that condition the wound site and the promotion of healing. Based on experience with critical and noncritical defect models in small and large animals, the potential advantages of this approach are discussed and experimental evidence of promoting bone formation is provided.