title: Adipose-derived stromal cells overexpressing vascular endothelial growth factor accelerate mouse excisional wound healing.
abstract: Angiogenesis is essential to wound repair, and vascular endothelial growth factor (VEGF) is a potent factor to stimulate angiogenesis. Here, we examine the potential of VEGF-overexpressing adipose-derived stromal cells (ASCs) for accelerating wound healing using nonviral, biodegradable polymeric vectors. Mouse ASCs were transfected with DNA plasmid encoding VEGF or green fluorescent protein (GFP) using biodegradable poly (β-amino) esters (PBAE). Cells transfected using Lipofectamine 2000, a commercially available transfection reagent, were included as controls. ASCs transfected using PBAEs showed enhanced transfection efficiency and 12-15-fold higher VEGF production compared with cells transfected using Lipofectamine 2000 (*P < 0.05). When transplanted into a mouse wild-type excisional wound model, VEGF-overexpressing ASCs led to significantly accelerated wound healing, with full wound closure observed at 8 days compared to 10-12 days in groups treated with ASCs alone or saline control (*P < 0.05). Histology and polarized microscopy showed increased collagen deposition and more mature collagen fibers in the dermis of wound beds treated using PBAE/VEGF-modified ASCs than ASCs alone. Our results demonstrate the efficacy of using nonviral-engineered ASCs to accelerate wound healing, which may provide an alternative therapy for treating many diseases in which wound healing is impaired.
authors.affiliation: Hagey Laboratory for Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Department of Surgery and Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Nauta
authors.forename: Catharina
authors.initials: C
authors.lastname: Seidel
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Deveza
authors.forename: Daniel
authors.initials: D
authors.lastname: Montoro
authors.forename: Monica
authors.initials: M
authors.lastname: Grova
authors.forename: Sae Hee
authors.initials: SH
authors.lastname: Ko
authors.forename: Jeong
authors.initials: J
authors.lastname: Hyun
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Gurtner
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D049109:Cell Proliferation; D002470:Cell Survival; D003094:Collagen / Q000378:metabolism; D017077:Culture Media, Conditioned; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic; D010957:Plasmids / Q000235:genetics; D011108:Polymers / Q000737:chemistry; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics*
chemical_list: D001672:Biocompatible Materials; D017077:Culture Media, Conditioned; D011108:Polymers; D042461:Vascular Endothelial Growth Factor A; C507253:poly(beta-amino ester); D049452:Green Fluorescent Proteins; D003094:Collagen