Adenoviral mediated gene transfer of PDGF-B enhances wound healing in type I and type II diabetic wounds
| Autor: | Anna B. Katz, Foong-Yen Lim, Philip W. Zoltick, Sundeep G. Keswani, Timothy M. Crombleholme, Antoneta Radu, Meenhard Herlyn, Datis Alaee |
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| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Genetic Vectors Dermatology Nod Streptozocin Adenoviridae Diabetes Mellitus Experimental Neovascularization Mice Mice Inbred NOD Internal medicine medicine Animals Receptors Platelet-Derived Growth Factor Probability Analysis of Variance Wound Healing integumentary system biology business.industry Growth factor Biopsy Needle Gene Transfer Techniques Granulation tissue Genetic Therapy Streptozotocin Immunohistochemistry Surgery Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Endocrinology Diabetes Mellitus Type 2 biology.protein Wounds and Injuries Female medicine.symptom business Wound healing Platelet-derived growth factor receptor medicine.drug Blood vessel |
| Zdroj: | Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society. 12(5) |
| ISSN: | 1067-1927 |
| Popis: | We have shown that the genetically diabetic mouse (C57BLKS/J-m+/+Lepr(db)) has a wound healing and neovascularization deficit associated with an inability to recruit endothelial precursor cells (EPCs) to the wound. This may account for a fundamental mechanism in impaired diabetic wound healing. We hypothesized that the adenoviral mediated overexpression of platelet-derived growth factor-B (PDGF-B) would enhance wound healing, improve neovascularization, and recruit EPCs to the epithelial wound in three diabetic mouse models. Eight-mm full-thickness flank wounds were made in db/db, nonobese NOD/Ltj, streptozotocin, and C57BLKS/J mice. Wounds were treated with either 1 x 10(8) PFU Ad-PDGF-B or Ad LacZ or phosphate buffered saline solution. Wounds harvested at seven days were analyzed for epithelial gap, blood vessel density, granulation tissue area, and EPCs per high powered field. All three diabetic models have a significant wound healing and neovascularization defect compared to C57BLKS/J controls. Adenoviral-PDGF-B treatment significantly enhanced epithelial gap closure in db/db, streptozotocin, and nonobese NOD/Ltj mice as compared to diabetic phosphate buffered saline solution or Ad LacZ controls. A similar increase in the formation of granulation tissue and vessel density was also observed. All three models had reduced levels of GATA-2 positive EPCs in the wound bed that was corrected by the adenoviral mediated gene transfer of PDGF. EPC recruitment was positively correlated with neovascularization and wound healing. Three different diabetic models have a wound healing impairment and a decreased ability to recruit EPCs. The vulnerary effect of adenoviral mediated gene therapy with PDGF-B significantly enhanced wound healing and neovascularization in diabetic wounds. The PDGF-B mediated augmentation of EPC recruitment to the wound bed may be a fundamental mechanism of these results. |
| Databáze: | OpenAIRE |
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