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Gene transfer in skin equivalnts and stem cells: novel strategies for chronic ulcer repair and tissue regeneration

Objective

Chronic ulcers and defective tissue repair represent a major health problem. Conventional therapeutic approaches are not sufficient to guarantee an adequate healing in chronic ulcers and recurrence is frequent. Among non conventional treatments, short p rotein half-life and inefficient delivery to target cells have been identified as main limitations of the topical application of recombinant growth factors. Similarly, the therapeutic effect of skin equivalent grafting was limited, in particular due to impaired production of granulation tissue by the host. The present project relays on the development and validation of novel therapeutic strategies for tissue regeneration, based on the use of genetically modified stem cells and skin equivalents. Th e plan structure starts with a multidisciplinary research approach aimed at characterising the role and mechanism of action of potentially therapeutic proteins. In parallel, a wide analysis will be conducted to exploit the most suitable adeno and adeno -associated viral vectors for gene transfer into selected cell types. The research will be then directed towards in-vivo application of genetically modified stem cells and ex-vivo engineered skin equivalents as delivery systems of therapeutic proteins. Safety and potential therapeutic effect will be tested on diabetic animals and/or other animal models of impaired wound healing. Optimized procedures for ex-vivo genetic modification of skin equivalents using adeno and/or adeno-associated viral vecto rs carrying genes with demonstrated therapeutic potential will be translated into Standard Operating Procedures (SOPs) to produce skin grafts for clinical use. The research will ultimately target the design of a Phase I clinical trial protocol for gene therapy of chronic diabetic ulcers unresponsive to conventional therapies.

Call for proposal

FP6-2003-LIFESCIHEALTH-I
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Coordinator

PROVINCIA ITALIANA DELLA CONGREGAZIONE DEI FIGLI DELL'IMMACOLATA CONCEZIONE - ISTITUTO DERMOPATICO DELL'IMMACOLATA - IRCCS'
Address
Via Dei Monti Di Creta, 104
Rome
Italy

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Participants (6)

CENTRO CARDIOLOGICO MONZINO - IRCCS
Italy
Address
Via Parea, 4
Milan

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EIDGENOSSISCHE TECHNISCHE HOCHSCHULE ZURICH
Switzerland
Address
Raemistrasse 101
Zurich

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UNIVERSITY OF COLOGNE - CLINICAL DEPARTMENT
Germany
Address
Joseph Stelzmann Str., 9
Cologne

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EUROPEAN MOLECULAR BIOLOGY LABORATORY
Germany
Address
Meyerhofstr. 1
Heidelberg

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IDI FARMACEUTICI SPA
Italy
Address
Via Dei Castelli Romani 83/85
Pomezia (Rm)

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Links
CENTRO DE INVESTIGACIONES ENERGÉTICAS MEDIOAMBIENTALES Y TECNOLÓGICAS
Spain
Address
Avda Complutense 22
Madrid

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