Search

Epidermolysis bullosa (EB) is a phenotypically diverse group of hereditary blistering disorders involving mutations in 20 different genes. Those debilitating disorders are currently incurable; however, there are a number of promising preclinical trials, where some treatments already approach the stage of early clinical trial. In this paper we introduce a novel surgical approach to the treatment of EB-induced ulcerations. The purpose of our study was to evaluate the safety and efficacy of a new biological dressing in the form of an allogenic human skin equivalent graft before using multipotent stem cells, classified as an advanced therapy medicinal product. Implanted human acellular dermal matrices were prepared from the superficial layers of donated human skin. Scaffold sterilization was conducted via irradiation with the use of a linear electron accelerator. Following water-knife debridement, wounds were surgically covered with accordingly prepared grafts and dressed in burn-injury fashion. Subsequently, the wounds were monitored for infection and viability. Our data indicate that grafting as a potential new medicinal product was safe and effective in patients with rare diseases, such as EB, and may be used for stem cells to create new Advanced Therapy Medicinal Products. During a 200-day follow-up, we proved the safety of using human scaffolds (allogeneic graft) by observing no apparent infection or necrosis. Instead, we noted fewer required dressing changes, promoted wound healing, pain reduction, and an overall improvement in the quality of life in patients with EB. The protocol for grafting allogenic acellular epidermal sheets is the most promising treatment for severely affected skin areas in EB patients to date. [ABSTRACT FROM AUTHOR]

Nonhealing wounds can be a major clinical problem. Impaired wound healing is often related to massive tissue injury, concomitant wound healing deficiencies (chronic wounds), burn injury, or congenital conditions. We propose a novel biological dressing as an alternative surgical approach. The dressing is a form of an allogenic human skin graft equivalent with further use of allogeneic stem cells classified as an advanced therapy medicinal product. This new allogenic acellular human skin graft has been specifically developed to address the clinical indications for dressing wound lesions and promoting tissue repair in specific rare genetic diseases. This case report illustrates the use of an acellular human skin allograft seeded with multipotent stem cells in the treatment of tissue injuries (burns), congenital conditions, and chronic wounds. Donor-tissue processing yields an acellular dermal matrix with integral collagen bundling and organization, as well as an intact basement membrane complex. Preclinical observations show prolonged viability of acellular human skin grafts with multipotent stem cells. This was confirmed with histological and electron-microscopic evaluation of biopsies, which demonstrated host-cell infiltration and neovascularization of the biological dressing. Moreover, the dressings were characterized by low immunogenicity, as confirmed by histology exam and T-cell proliferation assays in vitro. Our data confirmed the safety and efficacy of the evaluated acellular human skin grafts, which may be used in patients with rare diseases, such as epidermolysis bullosa, burn injuries, and chronic wounds. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is a phenolic compound being constituent of numerous everyday-used products. Additionally, good absorption through skin and gastrointestinal tract is an unquestionable evidence for high risk of BPA exposure and its possible influence on health. Effects of BPA action on cells and tissues are associated with its structural and functional similarities to steroid hormones. Here we investigated whether BPA could possibly influence immune cells through steroid receptors present on majority of these cells. In in vitro experiments with 200 nM and 1000 nM BPA concentrations we found that high levels affect activation of lymphocytes through increased CD25 expression, with no changes in functional response based on IFN-gamma production. We demonstrated that BPA influence not only phenotype of monocytes with increased frequency of CD14++CD16- subtypes, but also activation inhibition with decline of HLADR expression within monocytes. Similarly to lymphocytes, no changes were observed in context of monocytes function in BPA-exposed cells. Our study revealed that BPA actions are also associated with its direct role in modulation of immune system cells. We presume that further experiments would allow establishing connection between presented data and increased risk of cancer and metabolic diseases in subject exposed to bisphenol A. [ABSTRACT FROM AUTHOR]

Altered activities of ligands belonging to tumour necrosis factor (TNF) superfamily, namely B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL) and apoptosis inducing ligand (TRAIL) were demonstrated in several haematological diseases including acute lymphoblastic leukaemia (ALL). BAFF, APRIL and TRAIL provide crucial survival signals to immature, naive and activated B cells. These ligands are capable of activating a broad spectrum of intracellular signalling cascades that can either induce apoptosis or protect from programmed cell death. BAFF and APRIL, which can directly activate the NF-κB pathway, have been identified as crucial survival factors for ALL cells. Here, we have analyzed serum BAFF, APRIL and TRAIL concentrations in 48 patients with newly diagnosed ALL and 44 healthy volunteers. The levels of APRIL and BAFF were significantly higher in ALL patients as compared to healthy volunteers. In contrast, concentrations of TRAIL were significantly lower in ALL patients. Moreover, following induction, the levels of APRIL, but not BAFF or TRAIL, were significantly lower in a group of patients with complete remission (CR) as compared to non-respondent (NR) ALL patients. Furthermore, we demonstrated statistically significant differences in concentrations of APRIL between CR MRD-negative and CR, MRD-positive ALL patients. Notably detection of higher concentrations of APRIL was associated with shorter leukaemia-free survival and overall survival. Altogether, our data indicate that APRIL can play an important role in the pathogenesis of ALL and the measurement of APRIL levels can improve prognostication in ALL patients. [ABSTRACT FROM AUTHOR]