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Adenoviral mediated gene transfer of PDGF-B enhances wound healing in type I and type II diabetic wounds.
Wound Repair Regen 2004 Sep-Oct; 12(5):497-504WR

Abstract

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.

Authors+Show Affiliations

Division of General, Thoracic, and Fetal Surgery, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15453831

Citation

Keswani, Sundeep G., et al. "Adenoviral Mediated Gene Transfer of PDGF-B Enhances Wound Healing in Type I and Type II Diabetic Wounds." Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society, vol. 12, no. 5, 2004, pp. 497-504.
Keswani SG, Katz AB, Lim FY, et al. Adenoviral mediated gene transfer of PDGF-B enhances wound healing in type I and type II diabetic wounds. Wound Repair Regen. 2004;12(5):497-504.
Keswani, S. G., Katz, A. B., Lim, F. Y., Zoltick, P., Radu, A., Alaee, D., ... Crombleholme, T. M. (2004). Adenoviral mediated gene transfer of PDGF-B enhances wound healing in type I and type II diabetic wounds. Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society, 12(5), pp. 497-504.
Keswani SG, et al. Adenoviral Mediated Gene Transfer of PDGF-B Enhances Wound Healing in Type I and Type II Diabetic Wounds. Wound Repair Regen. 2004;12(5):497-504. PubMed PMID: 15453831.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adenoviral mediated gene transfer of PDGF-B enhances wound healing in type I and type II diabetic wounds. AU - Keswani,Sundeep G, AU - Katz,Anna B, AU - Lim,Foong-Yen, AU - Zoltick,Philip, AU - Radu,Antoneta, AU - Alaee,Datis, AU - Herlyn,Meenhard, AU - Crombleholme,Timothy M, PY - 2004/9/30/pubmed PY - 2005/2/3/medline PY - 2004/9/30/entrez SP - 497 EP - 504 JF - Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society JO - Wound Repair Regen VL - 12 IS - 5 N2 - 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. SN - 1067-1927 UR - https://www.unboundmedicine.com/medline/citation/15453831/Adenoviral_mediated_gene_transfer_of_PDGF_B_enhances_wound_healing_in_type_I_and_type_II_diabetic_wounds_ L2 - https://doi.org/10.1111/j.1067-1927.2004.12501.x DB - PRIME DP - Unbound Medicine ER -