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  Transient gene therapy to treat cutaneous radiation syndrome: development in a minipig model

Riccobono, D., Forcheron, F., Agay, D., Scherthan, H., Meineke, V., & Drouet, M. (2014). Transient gene therapy to treat cutaneous radiation syndrome: development in a minipig model. Health Physics, 106(6), 713-719. doi:10.1097/HP.0000000000000099.

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Riccobono, D., Author
Forcheron, F., Author
Agay, D., Author
Scherthan, H.1, 2, Author              
Meineke, V., Author
Drouet, M., Author
Affiliations:
1Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433549              
2Institut für Radiobiologie der Bundeswehr, Neuherbergstraße 11, 80937 München, Germany, ou_persistent22              

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Free keywords: Adipose Tissue/cytology Animals Disease Models, Animal Feasibility Studies Genetic Therapy/*methods Hedgehog Proteins/genetics Radiation Injuries, Experimental/*genetics/surgery/*therapy Skin/*injuries/*radiation effects Stem Cell Transplantation Stem Cells/cytology/metabolism Swine *Swine, Miniature Transfection
 Abstract: Cutaneous radiation syndrome is the delayed consequence of localized skin exposure to high doses of ionizing radiation. Adipocyte derived stem cells injection may improve tissue regeneration through secreted factors. Thus mesenchymal stem cells secretome optimization, using transient transfection, may represent a new strategy to treat this syndrome. Sonic hedgehog, a secreted protein involved in cell proliferation and angiogenesis, has been chosen as a first candidate. Here preliminary results are reported of the therapeutic potential of transient gene therapy to cure cutaneous radiation syndrome in a minipig model. Adipocyte derived stem cells were transiently transfected by electroporation with a plasmid coding for Sonic Hedgehog. Gottingen minipigs were locally irradiated using a (60)Co gamma source at the dose of 50 Gy and received Phosphate Buffer Salin (controls: n = 8), stem cells (50 x 10(6) each time, n = 5) or transfected stem cells (25+/-7 x 10(6) each time, n = 1). All controls exhibited a homogeneous clinical evolution of cutaneous radiation syndrome with final necrosis (day 91). In stem cell injected minipigs, an ultimate wound healing was observed in four out of five grafted animals (day 130 +/- 28, complete in two of them) (historical results). The Sonic hedgehog animal, albeit injected with a lower number of transfected stem cells, presented a very similar evolution of skin healing without necrosis or uncontrolble pain. Globally this preliminary report suggests that local injection of Sonic Hedgehog transfected adipocyte derived stem cells may improve wound healing. Thus work is ongoing to evaluate this therapeutic strategy on a larger number of animals.

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Language(s): eng - English
 Dates: 2014-06
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1097/HP.0000000000000099
ISSN: 1538-5159 (Electronic)0017-9078 (Print)
 Degree: -

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Title: Health Physics
Source Genre: Journal
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Publ. Info: Health Physics Society
Pages: - Volume / Issue: 106 (6) Sequence Number: - Start / End Page: 713 - 719 Identifier: -