Paracrine Activity from Adipose-Derived Stem Cells on In Vitro Wound Healing in Human Tympanic Membrane Keratinocytes.

Stem cell therapies for tympanic membrane repair have shown initial experimental success using mesenchymal stem cells in rat models to promote healing; however, the mechanisms providing this benefit are not known. We investigated in vitro the paracrine effects of human adipose-derived stem cells (ADSCs) on wound healing mechanisms for human tympanic membrane-derived keratinocytes (hTM) and immortalized human keratinocytes (HaCaT). ADSC conditioned media (CM) were assessed for paracrine activity on keratinocyte proliferation and migration, with hypoxic conditions for ADSC culture used to generate contrasting effects on cytokine gene expression.

Minireview: Extrapituitary prolactin: an update on the distribution, regulation, and functions.

Prolactin (PRL) is an important hormone with many diverse functions. Although it is predominantly produced by lactrotrophs of the pituitary there are a number of other organs, cells, and tissues in which PRL is expressed and secreted. The impact of this extrapituitary PRL (ePRL) on localized metabolism and cellular functions is gaining widespread attention.

The biocompatibility of silk fibroin and acellular collagen scaffolds for tissue engineering in the ear.

Recent experimental studies have shown the suitability of silk fibroin scaffold (SFS) and porcine-derived acellular collagen I/III scaffold (ACS) as onlay graft materials for tympanic membrane perforation repair. The aims of this study were to further characterize and evaluate the in vivo biocompatibility of SFS and ACS compared with commonly used materials such as Gelfoam and paper in a rat model. The scaffolds were implanted in subcutaneous (SC) tissue and middle ear (ME) cavity followed by histological and otoscopic evaluation for up to 26 weeks.

Prolactin expression in the cochlea of aged BALB/c mice is gender biased and correlates to loss of bone mineral density and hearing loss.

Prolactin is a versatile hormone with over 300 known functions and predominantly expressed in the pituitary. However, its expression has additionally been found in a number of extrapituitary organs. Recently, we described the expression of prolactin in the inner ear of mice, where it was correlated to age.

Tympanic membrane repair using silk fibroin and acellular collagen scaffolds.

Objectives/hypothesis: To evaluate the efficacy of silk fibroin scaffolds (SFS) and acellular collagen scaffolds (ACS) for the repair of tympanic membrane (TM) in a guinea pig acute perforation model.

Study Design: Experimental animal research.

Methods: Seventy-two albino guinea pigs underwent perforation of the right TM and were divided into four experimental groups (n = 18).

TGF-α/HA complex promotes tympanic membrane keratinocyte migration and proliferation via ErbB1 receptor.

Tympanic membrane perforations are common and represent a management challenge to clinicians. Current treatments for chronic perforations involve a graft surgery and require general anaesthesia, including associated costs and morbidities. Bioactive molecules (e.

Scaffolds for tympanic membrane regeneration in rats.

Tympanic membrane (TM) perforations lead to significant hearing loss and result in possible infection of the middle ear. Myringoplasty is commonly performed to repair chronic perforations. Although various grafts and materials have been used to promote TM regeneration, all have associated limitations.

Tissue engineering of the tympanic membrane.

Tympanic membrane (TM) perforations are common, with current treatments for chronic perforations involving surgery, using various graft materials, from autologous cartilage or fascia through to paper patch. Recent research developments in this field have begun applying the principles of tissue engineering, with appropriate scaffolds, cells, and bioactive molecules (BMs). This has revolutionized the therapeutic approach due to the availability of a wide range of materials with appropriate compatibility and mechanical properties to regenerate the membrane acoustics and may also represent a paradigm shift in the management of TM perforations in an outpatient setting without surgery.

Age related changes in gene expression within the cochlea of C57BL/6J mice.

Background And Aims: Hearing loss as a unique symptom is highly prevalent in the elderly and while there exists several pathologies that would result in age related hearing loss (ARHL), most agree it is multifactorial with environmental, metabolic and genetic components. However, no research to date has discovered a definitive genetic cause. This paper describes the use of microarray to address this issue.

A review on the use of hyaluronic acid in tympanic membrane wound healing.

Introduction: Tympanic membrane perforation represents a significant morbidity, especially if it occurs during a child's speech and language development. Recently, there has been an increased interest in hyaluronic-acid-related research and products as a potential therapeutic option for tympanic membrane perforation repair.

Areas Covered: This review describes the physical and chemical properties of hyaluronic acid and examines the role of hyaluronic acid in wound healing, in particular on the tympanic membrane.

In vitro cultured primary cells from a human utricle explant possesses hair cell like characteristics.

The utricle is the enlarged portion of the membranous labyrinth of the inner ear and is essential for balance. It comprises of fine hair cells (mechanoreceptors), supporting cells and calcareous otoliths. Utricle cells are considered to be post-mitotic and possess a limited capacity for regeneration.

Phenotypic and genotypic profile of human tympanic membrane derived cultured cells.

The human tympanic membrane (hTM), known more commonly as the eardrum, is a thin, multi-layered membrane that is unique in the body as it is suspended in air. When perforated, the hTM's primary function of sound-pressure transmission is compromised. For the purposes of TM reconstruction, we investigated the phenotype and genotype of cultured primary cells derived from hTM tissue explants, compared to epithelial (HaCaT cells) and mesenchymal (human dermal fibroblasts (HDF)) reference cells.

Preliminary results of the application of a silk fibroin scaffold to otology.

The surgical treatment to repair chronic tympanic membrane perforations is myringoplasty. Although multiple autologous grafts, allografts, and synthetic graft materials have been used over the years, no single graft material is superior for repairing all perforation types. Recently, the remarkable properties of silk fibroin protein have been studied, with biomedical and tissue engineering applications in mind, across a number of medical and surgical disciplines.

Novel cationic lipophilic peptides for oligodeoxynucleotide delivery.

In search of new oligodeoxynucleotide (ODN) delivery agents, we evaluated novel peptides derived from core peptide H-GLRILLLKV-OH (CP). CP is a fragment designed from the T-cell antigen receptor (TCR) alpha-chain transmembrane sequence. CP was able to enter cells including T-cells and inhibited interleukin-2 (IL-2) production.

Synthesis of a library of polycationic lipid core dendrimers and their evaluation in the delivery of an oligonucleotide with hVEGF inhibition.

This article follows on from our previous work in the area of non-viral gene delivery using polycationic dendrimers (PCDs). Herein we report on the synthesis and efficacy of a new library of lipid core PCDs in the delivery of the anti-angiogenic oligonucleotide (ODN-1) to retinal pigment epithelial cells. ELISA was used to monitor hVEGF levels in cells transfected with dendriplexes, Cytofectin GSV and control (non-transfected).

Treatments for choroidal and retinal neovascularization: a focus on oligonucleotide therapy and delivery for the regulation of gene function.

Blinding eye diseases caused by neovascularization of the retinal tissue are the leading cause of blindness in Western societies. Current treatments, such as laser photocoagulation, are limited in their effectiveness at halting the progression of angiogenesis and are unable to reduce the number of vessels once they have developed. In addition, although complete blindness is often avoided, vision is often permanently impaired by the treatment itself.

Inhibition of in vitro VEGF expression and choroidal neovascularization by synthetic dendrimer peptide mediated delivery of a sense oligonucleotide.

Ocular neovascularisation is the leading cause of blindness in developed countries and the most potent angiogenic factor associated with neovascularisation is vascular endothelial growth factor (VEGF). We have previously described a sense oligonucleotide (ODN-1) that possesses anti-human and rat VEGF activity. This paper describes the synthesis of lipid-lysine dendrimers and their subsequent ability to delivery ODN-1 to its target and mediate a reduction in VEGF concentration both in vitro and in vivo.

Discovery of a novel control element within the 5'-untranslated region of the vascular endothelial growth factor. Regulation of expression using sense oligonucleotides.

The regulation of vascular endothelial growth factor (VEGF), a potent stimulator of angiogenesis, is controlled primarily through the interactions of control elements located within the 5'- and 3'-untranslated regions, many of which are yet to be described. In this study we examined the 5'-untranslated region of human VEGF for control elements with the aim of regulating expression both in vitro and in vivo using oligonucleotide gene therapy. A potential control element was located, two sense oligonucleotides (S(1) and S(2)) were designed based on its sequence, and a third oligonucleotide (S(3)) was designed as a control and mapped to the 16 base pairs immediately upstream.

Syntheses of polycationic dendrimers on lipophilic peptide core for complexation and transport of oligonucleotides.

Synthesis of novel polycationic lipophilic peptide core(s) was accomplished and these agents successfully transfected human retinal pigment epithelium cells with ODN1 upon complexation with the oligonucleotide. The level of transfection was indirectly measured by the decreased production of the protein hVEGF (human vascular endothelial growth factor) in comparison to the transfection agent cytofectin GSV.