Collagen-embedded platelet-derived growth factor DNA plasmid promotes wound healing in a dermal ulcer model.
BACKGROUND
Gene therapy has shown limited efficacy for treating congenital diseases, partly due to temporary gene expression and host immune responses. Such results suggest that gene therapy is ideal for chronic wound treatment where limited duration of target gene expression is required. This study tested the wound healing effects of topically applied platelet-derived growth factor (PDGF)-A or -B chain DNA plasmids embedded within a collagen lattice.


METHODS
Four 6-mm dermal ulcer wounds were created in the ears of young adult New Zealand White rabbits made ischemic by division of the central and rostral arteries. Wounds were treated with lyophilized collagen containing PDGF-B DNA (1.0-3.0 mg), PDGF-A DNA (1.0 mg), irrelevant DNA (1.0 mg), or collagen alone. Wounds were dressed and harvested after 10 days for measurement of granulation tissue formation, epithelialization, and wound closure. Results were evaluated with a paired two-tailed Student t test, with P values < 0.05 considered significant.


RESULTS
PDGF-B DNA increased new granulation tissue (NGT) formation up to 52% and epithelialization 34% compared with controls. Wound closure was increased up to threefold. At 1.0 mg DNA, PDGF-A and PDGF-B stimulated similar responses. No difference in NGT or epithelialization was seen between control groups.


CONCLUSIONS
PDGF DNA gene therapy is effective at accelerating wound healing in ischemic dermal ulcers and provides a viable alternative to peptide growth factor therapy.
Tyrone
J W
JW
Division of Plastic and Reconstructive Surgery, Northwestern University, Ward Building, 19th Floor, 303 East Chicago Avenue, Chicago, Illinois 60611, USA.
Mogford
J E
JE
Chandler
L A
LA
Ma
C
C
Xia
Y
Y
Pierce
G F
GF
Mustoe
T A
TA
D000818:Animals; D003094:Collagen / Q000627:therapeutic use; D004247:DNA / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods; D010957:Plasmids / Q000008:administration & dosage* / Q000502:physiology / Q000627:therapeutic use; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics; D011817:Rabbits; D012883:Skin Ulcer / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D014945:Wound Healing / Q000502:physiology*
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C075278:platelet-derived growth factor A; D003094:Collagen; D004247:DNA