This proposal introduces the concept of treating the wound as an in vivo tissue culture which is achieved by enclosing the wound in a sealed chamber which functions as an in vivo incubator. Tissue repair in swine will be improved by adding culture medium, transplants of suspensions of skin cells and growth factors. The growth factors will be administered topically as peptides or into wound tissue by particle mediated gene transfer. This study may open new avenues in the treatment of chronic wounds as well as wounds with excessive healing such as hypertrophic scars and keloids.
The specific aims are: 1) to transplant keratinocyte suspensions and fibroblast suspensions in optimal cell numbers and to monitor with gene markers the repair process of epidermis and dermis; 2) to investigate if growth factors can be efficiently delivered by particle mediated gene transfer by in vivo or in vitro transfection (and transplantation) of autologous cells in order to provide an autocrine and paracrine source of peptide growth factors; 3) to investigate the effect of growth factors when delivered i) topically as peptides, ii) by in vivo gene transfer to wounds cells, or iii) by in vitro gene transfer to autologous cells which are transplanted to the wound as cell suspensions; and 4) to modify transgene persistence in the wound by transfection of cells with a resistant gene (neo) using an in vitro and in vivo selection environment.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Surgery, Anesthesiology and Trauma Study Section (SAT)
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Brigham and Women's Hospital
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Hackl, Florian; Bergmann, Juri; Granter, Scott R et al. (2012) Epidermal regeneration by micrograft transplantation with immediate 100-fold expansion. Plast Reconstr Surg 129:443e-452e
Koyama, Taro; Hackl, Florian; Aflaki, Pejman et al. (2011) A new technique of ex vivo gene delivery of VEGF to wounds using genetically modified skin particles promotes wound angiogenesis. J Am Coll Surg 212:340-8
Zuhaili, Baraa; Aflaki, Pejman; Koyama, Taro et al. (2010) Meshed skin grafts placed upside down can take if desiccation is prevented. Plast Reconstr Surg 125:855-65
Lu, Zheming; Brans, Richard; Akhrameyeva, Natali V et al. (2009) High-level expression of glycoprotein D by a dominant-negative HSV-1 virus augments its efficacy as a vaccine against HSV-1 infection. J Invest Dermatol 129:1174-84
Brans, Richard; Eriksson, Elof; Yao, Feng (2008) Immunization with a dominant-negative recombinant HSV type 1 protects against HSV-1 skin disease in guinea pigs. J Invest Dermatol 128:2825-32
Hirsch, Tobias; Spielmann, Malte; Velander, Patrik et al. (2008) Insulin-like growth factor-1 gene therapy and cell transplantation in diabetic wounds. J Gene Med 10:1247-52
Yao, Feng; Pomahac, Bohdan; Visovatti, Scott et al. (2007) Systemic and localized reversible regulation of transgene expression by tetracycline with tetR-mediated transcription repression switch. J Surg Res 138:267-74
Vranckx, Jan Jeroen; Hoeller, Daniela; Velander, Patrik E M et al. (2007) Cell suspension cultures of allogenic keratinocytes are efficient carriers for ex vivo gene transfer and accelerate the healing of full-thickness skin wounds by overexpression of human epidermal growth factor. Wound Repair Regen 15:657-64
Yao, Feng; Theopold, Christoph; Hoeller, Daniela et al. (2006) Highly efficient regulation of gene expression by tetracycline in a replication-defective herpes simplex viral vector. Mol Ther 13:1133-41
Augustinova, Hanka; Hoeller, Daniela; Yao, Feng (2004) The dominant-negative herpes simplex virus type 1 (HSV-1) recombinant CJ83193 can serve as an effective vaccine against wild-type HSV-1 infection in mice. J Virol 78:5756-65

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