کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6074333 | 1203484 | 2016 | 31 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Gene-Corrected Fibroblast Therapy for Recessive Dystrophic Epidermolysis Bullosa using a Self-Inactivating COL7A1 Retroviral Vector
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کلمات کلیدی
GFPGMPRDEBNHFself-inactivatingdermal-epidermal junction - اتصال پوستی-اپیدرمالsin - بدونDEJ - دژAnchoring fibril - فیبر لنگرNormal human fibroblasts - فیبروبلاستهای طبیعی انسانSkin equivalent - معادل پوستtype VII collagen - نوع کلاژن VIIgreen fluorescent protein - پروتئین فلورسنت سبزrecessive dystrophic epidermolysis bullosa - گلودرد اپیدرمولیز دیستروفی خونی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
امراض پوستی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Gene-Corrected Fibroblast Therapy for Recessive Dystrophic Epidermolysis Bullosa using a Self-Inactivating COL7A1 Retroviral Vector Gene-Corrected Fibroblast Therapy for Recessive Dystrophic Epidermolysis Bullosa using a Self-Inactivating COL7A1 Retroviral Vector](/preview/png/6074333.png)
چکیده انگلیسی
Patients with recessive dystrophic epidermolysis bullosa (RDEB) lack type VII collagen and therefore have severely impaired dermal-epidermal stability causing recurrent skin and mucosal blistering. There is currently no specific approved treatment for RDEB. We present preclinical data showing that intradermal injections of genetically corrected patient-derived RDEB fibroblasts using a Good Manufacturing Practices grade self-inactivating COL7A1 retroviral vector reverse the disease phenotype in a xenograft model in nude mice. We obtained 50% transduction efficiency in primary human RDEB fibroblasts with an average low copy number (range = 1-2) of integrated provirus. Transduced fibroblasts showed strong type VII collagen re-expression, improved adhesion properties, normal proliferative capabilities, and viability in vitro. We show that a single intradermal injection of 3 à 106 genetically corrected RDEB fibroblasts beneath RDEB skin equivalents grafted onto mice allows type VII collagen deposition, anchoring fibril formation at the dermal-epidermal junction, and improved dermal-epidermal adherence 2 months after treatment, supporting functional correction in vivo. Gene-corrected fibroblasts previously showed no tumorigenicity. These data show the efficacy and safety of gene-corrected fibroblast therapy using a self-inactivating vector that has now been good manufacturing grade-certified and pave the way for clinical translation to treat nonhealing wounds in RDEB patients.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Investigative Dermatology - Volume 136, Issue 7, July 2016, Pages 1346-1354
Journal: Journal of Investigative Dermatology - Volume 136, Issue 7, July 2016, Pages 1346-1354
نویسندگان
Joanna Jacków, Matthias Titeux, Soizic Portier, Soëli Charbonnier, Clarisse Ganier, Sonia Gaucher, Alain Hovnanian,