Molecular organization of the basement membrane zone

Hashmi, Sana; Marinkovich, M. Peter

doi:10.1016/j.clindermatol.2011.01.009

Cited by 48 publications

(39 citation statements)

References 163 publications

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“…1,2,3 The need for effective therapy is currently unmet and, despite attempts at protein, 1,2,3,4 bone marrow transplant, 5 cell 6,7 and induced pluripotent stem cells–based treatments, 8,9 palliative care remains the only option available. The most severe form of EB, often lethal by early childhood, is Herlitz-junctional EB (H-JEB), caused by mutations in the heterotrimer laminin-332, which plays a nonredundant role in epidermal–dermal adhesion by serving as a stable anchoring contact between the epidermal integrin receptors α3β1 and α6β6, and collagen VII, the main component of the dermal anchoring fibrils.…”

Section: Introductionmentioning

confidence: 99%

Somatic Correction of Junctional Epidermolysis Bullosa by a Highly Recombinogenic AAV Variant

et al. 2014

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Definitive correction of disease causing mutations in somatic cells by homologous recombination (HR) is an attractive therapeutic approach for the treatment of genetic diseases. However, HR-based somatic gene therapy is limited by the low efficiency of gene targeting in mammalian cells and replicative senescence of primary cells ex vivo, forcing investigators to explore alternative strategies such as retro- and lentiviral gene transfer, or genome editing in induced pluripotent stem cells. Here, we report correction of mutations at the LAMA3 locus in primary keratinocytes derived from a patient affected by recessive inherited Herlitz junctional epidermolysis bullosa (H-JEB) disorder using recombinant adenoassociated virus (rAAV)-mediated HR. We identified a highly recombinogenic AAV serotype, AAV-DJ, that mediates efficient gene targeting in keratinocytes at clinically relevant frequencies with a low rate of random integration. Targeted H-JEB patient cells were selected based on restoration of adhesion phenotype, which eliminated the need for foreign sequences in repaired cells, enhancing the clinical use and safety profile of our approach. Corrected pools of primary cells assembled functional laminin-332 heterotrimer and fully reversed the blistering phenotype both in vitro and in skin grafts. The efficient targeting of the LAMA3 locus by AAV-DJ using phenotypic selection, together with the observed low frequency of off-target events, makes AAV-DJ based somatic cell targeting a promising strategy for ex vivo therapy for this severe and often lethal epithelial disorder.

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Section: Introductionmentioning

confidence: 99%

Somatic Correction of Junctional Epidermolysis Bullosa by a Highly Recombinogenic AAV Variant

et al. 2014

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“…11,100 As an adaptation to the new extracellular environment in the wound as well as to the provisional basement membrane the keratinocytes assemble underneath themselves against the provisional wound matrix, there is a change in the expression levels and/or localization of the existing keratinocyte integrins and an induction of fibronectin-recognizing a 5 b 1 , a v b 1 , and a v b 6 integrins. 11 Expression of a v b 5 integrin in the migrating keratinocytes may depend on the severity of the trauma, as it is expressed in deep human and porcine excisional skin wounds, but not in smaller incisional human skin or oral mucosal wounds.…”

Section: 99mentioning

confidence: 99%

Integrins in Wound Healing

Koivisto

Heino

Häkkinen

et al. 2014

Advances in Wound Care

181

154

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“…The negative results of this study concerning the demonstration of nidogen-1 may be based on the fact that this ubiquitous component of the specialized extracellular matrix is not required for the overall architecture of the basement membrane. Only in development it plays an important role in BM stabilization, especially in tissues undergoing rapid growth or turnover (Ho et al, 2008;Hashmi and Marinkovich, 2011).…”

Section: Discussionmentioning

confidence: 99%

A Special Construction of Subepidermal Capillary Loops in the Hippopotamus (Hippopotamus amphibius)

Meyer

2012

Zoological Science

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Based on LM, TEM, and histochemical methods, the study describes the specific structure of subepidemal capillary loops in the integument of the hippopotamus (Hippopotamus amphibius). At 25- 60 µm, the diameter of the capillaries was more than twenty times larger than those found in other mammals, as was the diameter of the epidermal contact area of the hairpin turn, which had enlarged up to 200-400 µm(2). At about 13,400, the number of loops per cm(2) was three times higher than in the few other mammalian species measured to date. The remarkable sheath (thickness 2- 20 µm) of the capillary loops consists of a multitude of fine collagen IV fibres, which were in direct contact with the epidermal stratum (str.) basale, emphasizing an origin from the lamina fibroreticularis of the basement membrane. Additionally, the sheath contained many regions filled with free fatty acids. All observations confirmed the view that the walls of the subepidermal capillaries in the hippopotamus are adapted to withstand high blood pressure, permitting a high rate of blood vesselbased heat transfer from the periphery of the body. Until now this function is only known as an important thermoregulatory response in highly active mammals, e.g. dolphins. However, under hot climatic conditions but without strong exercise for cooling, such ability could be an effective and energy-saving procedure in semi-aquatic mammals.

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Molecular organization of the basement membrane zone

Cited by 48 publications

References 163 publications

Somatic Correction of Junctional Epidermolysis Bullosa by a Highly Recombinogenic AAV Variant

Somatic Correction of Junctional Epidermolysis Bullosa by a Highly Recombinogenic AAV Variant

Integrins in Wound Healing

A Special Construction of Subepidermal Capillary Loops in the Hippopotamus (Hippopotamus amphibius)

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