Effective healing of diabetic skin wounds by using nonviral gene therapy based on minicircle vascular endothelial growth factor DNA and a cationic dendrimer

The development of an efficient method to improve the wound healing process is urgently required for diabetic patients suffering a threat of limb amputations. Various growth factors have been proposed for treatment; however, more research still has to be carried out to maintain their curative effect. In the present study, we describe a simple nonviral gene therapy method for improving wound healing.

[1]  A. Boulton,et al.  The global burden of diabetic foot disease , 2005, The Lancet.

[2]  A T Hoogeveen,et al.  Efficacy of a peptide-based gene delivery system depends on mitotic activity. , 1996, Gene therapy.

[3]  D J Mooney,et al.  Spatiotemporal control of vascular endothelial growth factor delivery from injectable hydrogels enhances angiogenesis , 2007, Journal of thrombosis and haemostasis : JTH.

[4]  R. Duncan,et al.  The effect of dextrin-rhEGF on the healing of full-thickness, excisional wounds in the (db/db) diabetic mouse. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

[5]  C. Coutelle,et al.  An araC-controlled Bacterialcre Expression System to Produce DNA Minicircle Vectors for Nuclear and Mitochondrial Gene Therapy* , 2001, The Journal of Biological Chemistry.

[6]  A. Wellmann,et al.  Priming with a combination of proangiogenic growth factors improves wound healing in normoglycemic mice. , 2011, International journal of molecular medicine.

[7]  M. Kay,et al.  Minicircle DNA vectors devoid of bacterial DNA result in persistent and high-level transgene expression in vivo. , 2003, Molecular therapy : the journal of the American Society of Gene Therapy.

[8]  D. Scherman,et al.  Minicircle: an improved DNA molecule for in vitro and in vivo gene transfer , 1999, Gene Therapy.

[9]  C. Sheridan,et al.  Gene therapy finds its niche , 2011, Nature Biotechnology.

[10]  Jong-sang Park,et al.  Comparison between arginine conjugated PAMAM dendrimers with structural diversity for gene delivery systems. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[11]  M. Kwon,et al.  Cloning of Novel Epidermal Growth Factor (EGF) Plasmid for Gene Therapy on Diabetic Foot Ulcer , 2008 .

[12]  Y. Yatomi,et al.  Sphingosine 1-phosphate accelerates wound healing in diabetic mice. , 2007, Journal of dermatological science.

[13]  A. Palotie,et al.  Peripheral Blood Platelets Express VEGF-C and VEGF which Are Released during Platelet Activation , 1998, Thrombosis and Haemostasis.

[14]  H. Lee,et al.  Nonviral gene delivery to human ovarian cancer cells using arginine-grafted PAMAM dendrimer , 2011, Drug development and industrial pharmacy.

[15]  Dong-Eun Kim,et al.  Evaluation of generations 2, 3 and 4 arginine modified PAMAM dendrimers for gene delivery. , 2008, International journal of pharmaceutics.

[16]  Aleksander S. Popel,et al.  A compartment model of VEGF distribution in blood, healthy and diseased tissues , 2008, BMC Systems Biology.

[17]  S. W. Kim,et al.  Efficient expression of vascular endothelial growth factor using minicircle DNA for angiogenic gene therapy. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[18]  Vincent Falanga,et al.  Wound healing and its impairment in the diabetic foot , 2005, The Lancet.

[19]  H. Turndorf,et al.  The hyperalgesic effect of naloxone is attenuated in streptozotocin-diabetic mice , 2004, Psychopharmacology.

[20]  Xiaobing Fu,et al.  Research of PDGF-BB gel on the wound healing of diabetic rats and its pharmacodynamics. , 2008, The Journal of surgical research.

[21]  S. Schmidt,et al.  Effects of vascular endothelial growth factor on wound closure rates in the genetically diabetic mouse model , 2003, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[22]  Minhyung Lee,et al.  Enhanced transfection of primary cortical cultures using arginine-grafted PAMAM dendrimer, PAMAM-Arg. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[23]  M. Venermo,et al.  Treatment of diabetic foot ulcers. , 2009, The Journal of cardiovascular surgery.

[24]  Wei Zhi,et al.  Promotion of skin regeneration in diabetic rats by electrospun core-sheath fibers loaded with basic fibroblast growth factor. , 2011, Biomaterials.

[25]  A. Schor,et al.  Growth factors in the treatment of diabetic foot ulcers , 2003, The British journal of surgery.

[26]  E. Brogi,et al.  Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model. , 1994, The Journal of clinical investigation.

[27]  Jong-sang Park,et al.  Enhanced transfection efficiency of PAMAM dendrimer by surface modification with L-arginine. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[28]  E. Jude,et al.  The molecular biology of chronic wounds and delayed healing in diabetes , 2006, Diabetic medicine : a journal of the British Diabetic Association.

[29]  J. Porter,et al.  Therapeutic angiogenesis: time for the next phase. , 2000, Journal of the American College of Cardiology.

[30]  H. Dvorak,et al.  VPF/VEGF and the angiogenic response. , 2000, Seminars in perinatology.

[31]  C. Sheridan.  Erratum: Gene therapy finds its niche , 2011, Nature Biotechnology.