Lentiviral gene therapy with platelet-derived growth factor B sustains accelerated healing of diabetic wounds over time.
The treatment of diabetic wounds is a formidable clinical challenge. In this study, lentiviral vectors carrying the human platelet-derived growth factor B (PDGF-B) gene were used to treated diabetic mouse wounds. Full-thickness 2.0-cm x 2.0-cm excisional wounds were created on the dorsa of genetically diabetic C57BL/KsJ-m+/+Lepr(db) mice. Lentiviral vectors containing the PDGF-B gene were injected into the wound margins and base. Mice were killed at 14-, 21-, and 35-day intervals. Measurement of the residual epithelial gap showed a trend towards increased healing in lentiviral PDGF-treated wounds compared with untreated and saline-treated wounds at all time points. At 21 days, there was significantly increased healing in lentiviral PDGF-treated wounds (0.98+/-0.17 cm) compared with saline-treated wounds (1.22+/-0.30 cm; P<0.05). Immunohistochemistry for CD31 revealed significantly increased neovascularization in lentiviral PDGF-treated wounds compared with untreated and saline-treated wounds at 14 and 21 days (P<0.01). Picrosirius red staining demonstrated thicker and more highly organized collagen fibers in treated wounds compared with untreated and saline-treated wounds. Quantitative analysis of collagen content showed a 3.5-fold and 2.3-fold increase in lentiviral PDGF-treated wounds versus untreated and saline-treated wounds, respectively (P<0.01). Lentiviral gene therapy with PDGF-B can sustain diabetic wound healing over time and may possess promising potential in the clinical setting.
Division of Plastic and Reconstructive Surgery, New York Presbyterian Hospital, Columbia-Presbyterian Medical Center, Columbia University College of Physicians and Surgeons, New York, NY 10021, USA.
Li-Xing
LX
Man
Juliet C
JC
Park
Michael J
MJ
Terry
James M
JM
Mason
Whitney A
WA
Burrell
Fangjun
F
Liu
Brent Y
BY
Kimball
Sameer M
SM
Moorji
James A
JA
Lee
Arnold S
AS
Breitbart
D000704:Analysis of Variance; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000503:physiopathology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007124:Immunoenzyme Techniques; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D013194:Staining and Labeling; D014945:Wound Healing / Q000235:genetics*
D020574:Proto-Oncogene Proteins c-sis