Dystrophic epidermolysis bullosa (DEB) is a severe skin fragility disorder associated with trauma-induced blistering, progressive soft tissue scarring, and increased risk of skin cancer. DEB is caused by mutations in type VII collagen. In this study, we describe the generation of a collagen VII hypomorphic mouse that serves as an immunocompetent animal model for DEB. These mice expressed collagen VII at about 10% of normal levels, and their phenotype closely resembled characteristics of severe human DEB, including mucocutaneous blistering, nail dystrophy, and mitten deformities of the extremities. The oral blistering experienced by these mice resulted in growth retardation, and repeated blistering led to excessive induction of tissue repair, causing TGF-β1-mediated contractile fibrosis generated by myofibroblasts and pseudosyndactyly in the extremities. Intradermal injection of WT fibroblasts resulted in neodeposition of collagen VII and functional restoration of the dermal-epidermal junction. Treated areas were also resistant to induced frictional stress. In contrast, untreated areas of the same mouse showed dermal-epidermal separation following induced stress. These data demonstrate that fibroblast-based treatment can be used to treat DEB in a mouse model and suggest that this approach may be effective in the development of clinical therapeutic regimens for patients with DEB.
IntroductionSkin integrity and resistance to mechanical stress rely on the function of the dermal-epidermal junction zone (DEJZ), which anchors the epidermis to the underlying dermal matrix. The supramolecular cell adhesion complexes at the DEJZ mediate interactions of the cytoskeleton in basal keratinocytes with the basement membrane and the extracellular anchoring fibrils, which emanate from the basement membrane into the dermis and entrap dermal collagen bundles, thus establishing stable dermal-epidermal cohesion (1).The main component of the anchoring fibrils is collagen VII, a homotrimeric collagen synthesized by keratinocytes and fibroblasts (2). Fibril formation and deposition at the DEJZ requires proteolytic processing of procollagen VII to mature collagen (3). Loss of collagen VII functions in dystrophic epidermolysis bullosa (DEB) leads to absence or anomalies of the anchoring fibrils and to dermal-epidermal tissue separation. DEB refers to a clinically heterogeneous group of disorders including recessively and dominantly inherited subtypes (4, 5). All forms of DEB are allelic and caused by mutations in the collagen VII gene, COL7A1. Early investigations demonstrated reduced amounts of anchoring fibrils and collagen VII in the skin of patients with mild and moderate, reces-
The high correlation between the introduced gagCEST method and (23)Na imaging implies that gagCEST is a potentially useful biomarker for glycosaminoglycans.
Until very recently, the study of neural architecture using fixed tissue has been a major scientific focus of neurologists and neuroanatomists. A non-invasive detailed insight into the brain's axonal connectivity in vivo has only become possible since the development of diffusion tensor magnetic resonance imaging (DT-MRI). This unique approach of analyzing axonal projections in the living brain was used in the present study to describe major white matter fiber tracts of the mouse brain and also to identify for the first time non-invasively the rich connectivity between the amygdala and different target regions. To overcome the difficulties associated with high spatially and temporally resolved DT-MRI measurements a 4-shot diffusion weighted spin echo (SE) echo planar imaging (EPI) protocol was adapted to mouse brain imaging at 9.4T. Diffusion tensor was calculated from data sets acquired by using 30 diffusion gradient directions while keeping the acquisition time at 91 min. Two fiber tracking algorithms were employed. A deterministic approach (fiber assignment by continuous tracking - FACT algorithm) allowed us to identify and generate the 3D representations of various neural pathways. A probabilistic approach was further used for the generation of probability maps of connectivity with which it was possible to investigate - in a statistical sense - all possible connecting pathways between selected seed points. We show here applications to determine the connection probability between regions belonging to the visual or limbic systems. This method does not require a priori knowledge about the projections' trajectories and is shown to be efficient even if the investigated pathway is long or three-dimensionally complex. Additionally, high resolution images of rotational invariant parameters of the diffusion tensor, such as fractional anisotropy, volume ratio or main eigenvalues allowed quantitative comparisons in-between regions of interest (ROIs) and showed significant differences between various white matter regions.
A new technique for acquiring T 2 -weighted, balanced steadystate free precession (b-SSFP) images is presented. Based on the recently proposed transition into driven equilibrium (TIDE) method, T 2 -TIDE uses a special flip angle scheme to achieve T 2 -weighted signal decay during the transient phase. In combination with half-Fourier image acquisition, T 2 -weighted images can be obtained using
Purpose: To evaluate a new isotropic 3D proton-density, turbo-spin-echo sequence with variable flip-angle distribution (PD-SPACE) sequence compared to an isotropic 3D true-fast-imaging with steady-state-precession (True-FISP) sequence and 2D standard MR sequences with regard to the new 3D magnetic resonance observation of cartilage repair tissue (MOCART) score.
Materials and Methods:Sixty consecutive MR scans on 37 patients (age: 32.8 6 7.9 years) after matrix-associated autologous chondrocyte transplantation (MACT) of the knee were prospectively included. The 3D MOCART score was assessed using the standard 2D sequences and the multiplanar-reconstruction (MPR) of both isotropic sequences. Statistical, Bonferroni-corrected correlation as well as subjective quality analysis were performed.Results: The correlation of the different sequences was significant for the variables defect fill, cartilage interface, bone interface, surface, subchondral lamina, chondral osteophytes, and effusion (Pearson coefficients 0.514-0.865). Especially between the standard sequences and the 3D True-FISP sequence, the variables structure, signal intensity, subchondral bone, and bone marrow edema revealed lower, not significant, correlation values (0.242-0.383). Subjective quality was good for all sequences (P ! 0.05). Artifacts were most often visible on the 3D True-FISP sequence (P < 0.05).Conclusion: Different isotropic sequences can be used for the 3D evaluation of cartilage repair with the benefits of isotropic 3D MRI, MPR, and a significantly reduced scan time, where the 3D PD-SPACE sequence reveals the best results.
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