title: Comparison of Treatments With Local Mesenchymal Stem Cells and Mesenchymal Stem Cells With Increased Vascular Endothelial Growth Factor Expression on Irradiation Injury of Expanded Skin.
abstract: BACKGROUND
  Radiation injury results in chronically ischemic tissue. Radionecrosis can be encountered in severe cases. Mesenchymal stem cells (MSCs) have a therapeutic effect on ischemia-related lesions. In here, effects of bone-marrow derived MSC and vascular endothelial growth factor (VEGF) gene-transfected MSC (VEGF-MSC) treatment on expanded skin with irradiation injury is investigated.
  
  
  METHODS
  Silicone tissue expander (50 cm) was placed subcutaneously and expanded weekly up to 60 cm in 24 Sprague Dawley rats. Single fraction (30 Gy) radiotherapy was applied to the 2 × 2 cm area of the expanded skin. Dulbecco modified Eagle medium without cell component, MSCs, and VEGF-MSCs were injected subcutaneously at the irradiation-expansion sites. Skin samples were evaluated by histomorphometry and immunohistochemistry. Perfusion rate of the samples was assessed by scintigraphy.
  
  
  RESULTS
  Epidermal thickness of irradiated-expanded skin was increased after MSC and VEGF-MSC treatments, whereas dermal and capsule thicknesses did not change. The MSC and VEGF-MSC treatments were effective in preserving, respectively, CD31 and VEGF expressions at a similar level as expanded skin after irradiation injury. The VEGF-MSC treatment significantly elevated CD31 levels in the irradiated tissue. Skin perfusion results were consistent with the CD31 and VEGF expressions. The MSC and VEGF-MSC treatments were effective in increasing proliferating cell nuclear antigen (PCNA) expression in irradiation zone. The VEGF-MSC treatment was efficient in reducing both expansion- and irradiation-related apoptosis.
  
  
  CONCLUSIONS
  Vascular impairment and dermal insufficiency due to tissue expansion and irradiation injury can easily result in a wound hard to repair. The MSCs and VEGF-MSCs can promote neovascularization, reverse the effect of irradiation, and provide more durable soft tissue for expansion/implant reconstruction.
authors.affiliation: From the *Department of Plastic, Reconstructive Surgery and Burn Unit, Haydarpasa Training Hospital, Gulhane Military Medical Academy, Istanbul; †Department of Plastic and Reconstructive Surgery, Kocaeli University Medical Faculty, Kocaeli; ‡Department of Pathology, Haydarpasa Training Hospital, Gulhane Military Medical Academy, Istanbul; §Kocaeli University Institute of Health Sciences Center for Stem Cell and Gene Therapies; and ∥Department of Radiation Oncology, Kocaeli University Medical Faculty, Kocaeli, Turkey.
authors.forename: Sinan
authors.initials: S
authors.lastname: Öksüz
authors.forename: Murat Şahin
authors.initials: MŞ
authors.lastname: Alagöz
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Karagöz
authors.forename: Zafer
authors.initials: Z
authors.lastname: Küçükodac
authors.forename: Erdal
authors.initials: E
authors.lastname: Karaöz
authors.forename: Gökhan
authors.initials: G
authors.lastname: Duruksu
authors.forename: Görkem
authors.initials: G
authors.lastname: Aksu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000098:blood supply / Q000528:radiation effects*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A