Mechanism of Sustained Release of Vascular Endothelial Growth Factor in Accelerating Experimental Diabetic Healing

被引:138
作者
Brem, Harold [1 ]
Kodra, Arber
Golinko, Michael S.
Entero, Hyacinth
Stojadinovic, Olivera [2 ]
Wang, Vincent M. [3 ]
Sheahan, Claudia M. [4 ]
Weinberg, Alan D. [5 ]
Woo, Savio L. C. [6 ]
Ehrlich, H. Paul [7 ]
Tomic-Canic, Marjana [2 ]
机构
[1] New York Univ, Sch Med, Dept Surg,Helen & Martin Kimmel Wound Ctr, Div Wound Healing & Regenerat Med,Ranson Lab, New York, NY 10016 USA
[2] Univ Miami, Miller Sch Med, Dept Dermatol, Miami, FL 33136 USA
[3] Rush Univ, Med Ctr, Dept Orthoped Surg, Chicago, IL 60612 USA
[4] Louisiana State Univ, Hlth Sci Ctr, Dept Surg, New Orleans, LA USA
[5] Mt Sinai Sch Med, Dept Hlth Policy, New York, NY USA
[6] Mt Sinai Sch Med, Dept Gene & Cell Med, New York, NY USA
[7] Penn State Univ, Med Ctr, Div Plast Surg, Dept Surg, Hershey, PA USA
基金
美国国家卫生研究院;
关键词
MEDIATED GENE-TRANSFER; CORONARY-ARTERY-DISEASE; WOUND REPAIR; FOOT ULCERS; STIMULATES ANGIOGENESIS; CLINICAL-EVALUATION; HINDLIMB ISCHEMIA; LOCAL-DELIVERY; RAT HINDLIMB; VEGF121; CDNA;
D O I
10.1038/jid.2009.26
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
In this study, we hypothesize that local sustained release of vascular endothelial growth factor (VEGF), using adenovirus vector (ADV)-mediated gene transfer, accelerates experimental wound healing. This hypothesis was tested by determining the specific effects of VEGF(165) application on multiple aspects of the wound healing process, that is, time to complete wound closure and skin biomechanical properties. After showing accelerated wound healing in vivo, we studied the mechanism to explain the findings on multiple aspects of the wound healing cascade, including epithelialization, collagen deposition, and cell migration. Intradermal treatment of wounds in non-obese diabetic and db/db mice with ADV/VEGF(165) improves healing by enhancing tensile stiffness and/or increasing epithelialization and collagen deposition, as well as by decreasing time to wound closure. VEGF(165), in vitro, stimulates the migration of cultured human keratinocytes and fibroblasts, thus revealing a non-angiogenic effect of VEGF on wound closure. In conclusion, ADV/VEGF is effective in accelerating wound closure by stimulating angiogenesis, epithelialization, and collagen deposition. In the future, local administration and sustained, controlled release of VEGF(165) may decrease amputations in patients with diabetic foot ulcers and possibly accelerate closure of venous ulcers and pressure ulcers.
引用
收藏
页码:2275 / 2287
页数:13
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