Accelerated diabetic wound healing using cultured dermal fibroblasts retrovirally transduced with the platelet-derived growth factor B gene

被引:35
作者
Breitbart, AS
Laser, J
Parrett, B
Porti, D
Grant, RT
Grande, DA
Mason, JM
机构
[1] Columbia Univ Coll Phys & Surg, Columbia Presbyterian Med Ctr, New York Presbyterian Hosp, Div Plast & Reconstruct Surg, New York, NY 10032 USA
[2] N Shore Long Isl Jewish Res Inst, Gene Therapy Vector Lab, Manhasset, NY USA
[3] N Shore Long Isl Jewish Res Inst, Orthopaed Res Lab, Manhasset, NY USA
关键词
D O I
10.1097/01.SAP.0000084461.83554.71
中图分类号
R61 [外科手术学];
学科分类号
摘要
The treatment of diabetic wounds is a considerable clinical challenge. In this study, mouse dermal fibroblasts retrovirally transduced with the human platelet-derived growth factor B (PDGF-B) gene were used to treat diabetic mouse wounds. The PDGF-B gene was obtained from human umbilical vein endothelial cells, cloned into retroviral vectors, and introduced into diabetic mouse C57B1/ks-db/db dermal fibroblasts. In vitro results demonstrated production of PDGF-B protein by these transduced cells at steady-state levels of 1000 ng PDGF-B/10(6) cells/24 hours, and expression of PDGF-B mRNA. These cells were seeded onto polyglycolic acid scaffold matrices and used to treat diabetic mouse 20-mm X 20-mm full-thickness excisional dorsal skin wounds. Measurement of the residual epithelial gap at 21 days showed significantly accelerated healing (P < 0.05) of wounds treated with PDGF-transduced cells (epithelial gap 10.46 +/- 1.20 mm) compared with untreated wounds (14.66 +/- 0.591 mm), wounds treated with polyglycolic acid alone (14.80 +/- 0.575 mm), or wounds treated with negative control LNCX-transduced cells (13.76 +/- 0.831 mm). Immunohistochemical staining showed intense staining for PDGF in wounds treated with PDGF-B-transduced cells. This study demonstrates the promising potential for gene therapy in diabetic wound healing.
引用
收藏
页码:409 / 414
页数:6
相关论文
共 26 条
[1]  
ALBERTSON S, 1993, SURGERY, V114, P368
[2]   Inhibition of lipid peroxidation restores impaired vascular endothelial growth factor expression and stimulates wound healing and angiogenesis in the genetically diabetic mouse [J].
Altavilla, D ;
Saitta, A ;
Cucinotta, D ;
Galeano, M ;
Deodato, B ;
Colonna, M ;
Torre, V ;
Russo, G ;
Sardella, A ;
Urna, G ;
Campo, GM ;
Cavallari, V ;
Squadrito, G ;
Squadrito, F .
DIABETES, 2001, 50 (03) :667-674
[3]   IN-VIVO TRANSFER AND EXPRESSION OF A HUMAN EPIDERMAL GROWTH-FACTOR GENE ACCELERATES WOUND REPAIR [J].
ANDREE, C ;
SWAIN, WF ;
PAGE, CP ;
MACKLIN, MD ;
SLAMA, J ;
HATZIS, D ;
ERIKSSON, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (25) :12188-12192
[4]   Gene-enhanced tissue engineering: Applications for bone healing using cultured periosteal cells transduced retrovirally with the BMP-7 gene [J].
Breitbart, AS ;
Grande, DA ;
Mason, JM ;
Barcia, M ;
James, T ;
Grant, RT .
ANNALS OF PLASTIC SURGERY, 1999, 42 (05) :488-495
[5]   Treatment of ischemic wounds using cultured dermal fibroblasts transduced retrovirally with PDGF-B and VEGF121 genes [J].
Breitbart, AS ;
Grande, DA ;
Laser, J ;
Barcia, M ;
Porti, D ;
Malhotra, S ;
Kogon, A ;
Grant, RT ;
Mason, JM .
ANNALS OF PLASTIC SURGERY, 2001, 46 (05) :555-561
[6]   Gene-enhanced tissue engineering: Applications for wound healing using cultured dermal fibroblasts transduced retrovirally with the PDGF-B gene [J].
Breitbart, AS ;
Mason, JM ;
Urmacher, C ;
Barcia, M ;
Grant, RT ;
Pergolizzi, RG ;
Grande, DA .
ANNALS OF PLASTIC SURGERY, 1999, 43 (06) :632-639
[7]   PDGF AND TGF-ALPHA ACT SYNERGISTICALLY TO IMPROVE WOUND-HEALING IN THE GENETICALLY DIABETIC MOUSE [J].
BROWN, RL ;
BREEDEN, MP ;
GREENHALGH, DG .
JOURNAL OF SURGICAL RESEARCH, 1994, 56 (06) :562-570
[8]  
COLEMAN DL, 1982, DIABETES, V31, P1
[9]   Targeted expression of insulin-like growth factor to human keratinocytes: Modification of the autocrine control of keratinocyte proliferation [J].
Eming, SA ;
Snow, RG ;
Yarmush, ML ;
Morgan, JR .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1996, 107 (01) :113-120
[10]  
Greenhalgh David G., 1993, Wound Repair and Regeneration, V1, P69