Accelerated diabetic wound healing using cultured dermal fibroblasts retrovirally transduced with the platelet-derived growth factor B gene.
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.
Breitbart
Arnold S
AS
Division of Plastic and Reconstructive Surgery, New York Presbyterian Hospital, Columbia-Presbyterian Center, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. ab817@columbia.edu
Laser
Jordan
J
Parrett
Brian
B
Porti
Debra
D
Grant
Robert T
RT
Grande
Daniel A
DA
Mason
James M
JM
D000818:Animals; D020405:Dermis / Q000166:cytology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D005347:Fibroblasts / Q000166:cytology; D015316:Genetic Therapy; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics; D012190:Retroviridae; D014161:Transduction, Genetic; D014945:Wound Healing / Q000235:genetics*
D020574:Proto-Oncogene Proteins c-sis