Treatment of two patients with Herlitz junctional epidermolysis bullosa with artificial skin bioequivalents

Qiu, Jiang; Izakovic, Jan; Zenker, Martin; Fartasch, Manigé; Meneguzzi, Guerríno; Rascher, Wolfgang; Schneider, Holm

doi:10.1067/mpd.2002.127794

Cited by 22 publications

(9 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In all cases, the patient had a history of skin blistering starting at birth or shortly thereafter and leading to death within the first 3 years of life. Diagnostic skin biopsy specimens were obtained from all patients and subjected to immunofluorescence analysis with a panel of antibodies recognising different components of the epidermal BMZ as described previously (Jiang et al 2002). The clinical course was followed and documented for each patient.…”

Section: Methodsmentioning

confidence: 99%

Novel and recurrent mutations in the laminin-5 genes causing lethal junctional epidermolysis bullosa: molecular basis and clinical course of Herlitz disease

et al. 2004

Self Cite

View full text Add to dashboard Cite

Herlitz disease (H-JEB), the lethal form of junctional epidermolysis bullosa, is a rare genodermatosis presenting from birth with widespread erosions and blistering of skin and mucosae because of tissue cleavage within the epidermal basement membrane. Mutations in any of the three genes encoding the alpha3, beta3 and gamma2 chains of laminin-5 underlie this recessively inherited disorder. Here, we report the molecular basis and clinical course of H-JEB in 12 patients. Two novel nonsense mutations in the gene LAMA3 (E281X and K1299X) and a novel frame-shift mutation in the gene LAMB3 (1628insG) leading to a premature termination codon were identified by DNA sequencing and confirmed by restriction fragment length polymorphism analysis. In the four patients affected, neither the resulting truncated polypeptide chains nor assembled laminin-5 protein were detectable by immunofluorescence. Three patients were found to be heterozygous for the known hotspot mutation R635X and the recurrent mutations Q373X or 29insC in the gene LAMB3, whereas five others were homozygous for R635X. Significant variations in the disease progression and survival times between 1 and 30 months in this group of H-JEB patients emphasised the impact of modifying factors and the importance of immunostaining or mRNA assessment as parallel diagnostic methods. Interestingly, the only patients who survived for longer than 6 months were four females carrying the mutation R635X homozygously. In one of them, the clinical course may have been improved by treatment with artificial skin equivalents. These data may stimulate further investigation of genotype-phenotype correlations and facilitate mutation analysis and genetic counselling of affected families.

show abstract

Section: Methodsmentioning

confidence: 99%

Novel and recurrent mutations in the laminin-5 genes causing lethal junctional epidermolysis bullosa: molecular basis and clinical course of Herlitz disease

et al. 2004

Self Cite

View full text Add to dashboard Cite

show abstract

“…Owing to the density of hair follicles and elasticity of canine skin, the grafting technique used for our clinical protocol demanded partial excision of the dermis with removal of hair bulbs from the recipient bed, which implies ablation of the sebaceous glands and sweat glands. Such an invasive procedure is not required in human patients, in whom a laser de-epithelialization of the area to be grafted is sufficient to adequately receive genetically modified keratinocytes (Jiang et al, 2002;Mavilio et al, 2006), which circumvents any risk of contraction caused by ablation of the superficial dermis. Interestingly, the genetically modified grafts displayed a normal clinical aspect already 1 month after transplantation, with a stratified epidermis undergoing a canonical keratinization process, and colonization by melanocytes, endothelial, and dendritic cells.…”

Section: Permanent Expression At the Therapeutic Level Of The Exogenomentioning

confidence: 98%

Correction of Dog Dystrophic Epidermolysis Bullosa by Transplantation of Genetically Modified Epidermal Autografts

Gache

Gagnoux‐Palacios

et al. 2011

Journal of Investigative Dermatology

Self Cite

View full text Add to dashboard Cite

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin blistering condition caused by mutations in the gene coding for collagen type VII. Genetically engineered RDEB dog keratinocytes were used to generate autologous epidermal sheets subsequently grafted on two RDEB dogs carrying a homozygous missense mutation in the col7a1 gene and expressing baseline amounts of the aberrant protein. Transplanted cells regenerated a differentiated and vascularized auto-renewing epidermis progressively repopulated by dendritic cells and melanocytes. No adverse immune reaction was detected in either dog. In dog 1, the grafted epidermis firmly adhered to the dermis throughout the 24-month follow-up, which correlated with efficient transduction (100%) of highly clonogenic epithelial cells and sustained transgene expression. In dog 2, less efficient (65%) transduction of primary keratinocytes resulted in a loss of the transplanted epidermis and graft blistering 5 months after transplantation. These data provide the proof of principle for ex vivo gene therapy of RDEB patients with missense mutations in collagen type VII by engraftment of the reconstructed epidermis, and demonstrate that highly efficient transduction of epidermal stem cells is crucial for successful gene therapy of inherited skin diseases in which correction of the genetic defect confers no major selective advantage in cell culture.

show abstract

“…In addition, based on the intense search for stem cell sources that would avoid the ethical and biological issues (use of allogeneic cells) associated with hESCs, the idea became prevalent that BMSCs (and other 'MSCs') are pluripotent [25,26]. This new twist emerged from early studies that aimed to treat generalized disorders of the skeleton and other mesodermal tissues by systemic infusion or direct orthotopic injection of BMSCs.…”

Section: Stromal Stem/progenitor Cells (Also Known As 'Mesenchymal Stmentioning

confidence: 99%

Postnatal Stem Cells in Tissue Engineering

Robey

Bianco

2014

Principles of Tissue Engineering

View full text Add to dashboard Cite

Treatment of two patients with Herlitz junctional epidermolysis bullosa with artificial skin bioequivalents

Cited by 22 publications

References 20 publications

Novel and recurrent mutations in the laminin-5 genes causing lethal junctional epidermolysis bullosa: molecular basis and clinical course of Herlitz disease

Novel and recurrent mutations in the laminin-5 genes causing lethal junctional epidermolysis bullosa: molecular basis and clinical course of Herlitz disease

Correction of Dog Dystrophic Epidermolysis Bullosa by Transplantation of Genetically Modified Epidermal Autografts

Postnatal Stem Cells in Tissue Engineering

Contact Info

Product

Resources

About