title: Lipotransfer for radiation-induced skin fibrosis.
abstract: BACKGROUND
  Radiation-induced fibrosis (RIF) is a late complication of radiotherapy that results in progressive functional and cosmetic impairment. Autologous fat has emerged as an option for soft tissue reconstruction. There are also sporadic reports suggesting regression of fibrosis following regional lipotransfer. This systematic review aimed to identify cellular mechanisms driving RIF, and the potential role of lipotransfer in attenuating these processes.
  
  
  METHODS
  PubMed, OVID and Google Scholar databases were searched to identify all original articles regarding lipotransfer for RIF. All articles describing irradiated fibroblast or myofibroblast behaviour were included. Data elucidating the mechanisms of RIF, role of lipotransfer in RIF and methods to quantify fibrosis were extracted.
  
  
  RESULTS
  Ninety-eight studies met the inclusion criteria. A single, definitive model of RIF is yet to be established, but four cellular mechanisms were identified through in vitro studies. Twenty-one studies identified connective tissue growth factor and transforming growth factor β1 cytokines as drivers of fibrotic cascades. Hypoxia was demonstrated to propagate fibrogenesis in three studies. Oxidative stress from the release of reactive oxygen species and free radicals was also linked to RIF in 11 studies. Purified autologous fat grafts contain cellular and non-cellular properties that potentially interact with these processes. Six methods for quantifying fibrotic changes were evaluated including durometry, ultrasound shear wave elastography, thermography, dark field imaging, and laser Doppler and laser speckle flowmetry.
  
  
  CONCLUSIONS
  Understanding how lipotransfer causes regression of RIF remains unclear; there are a number of new hypotheses for future research.
authors.affiliation: Division of Surgery and Interventional Science, Royal Free Campus, London, UK.|Charles Wolfson Centre for Reconstructive Surgery, Royal Free Hospital, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Division of Surgery and Interventional Science, Royal Free Campus, London, UK.|Department of Plastic and Reconstructive Surgery, Royal Free Hospital, London, UK.|Charles Wolfson Centre for Reconstructive Surgery, Royal Free Hospital, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Griffin
authors.affiliation: Division of Surgery and Interventional Science, Royal Free Campus, London, UK.|Charles Wolfson Centre for Reconstructive Surgery, Royal Free Hospital, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Adigbli
authors.affiliation: Head and Neck Unit, Macmillan Cancer Centre, University College London Hospital, London, UK.|Charles Wolfson Centre for Reconstructive Surgery, Royal Free Hospital, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Kalavrezos
authors.affiliation: Division of Surgery and Interventional Science, Royal Free Campus, London, UK.|Head and Neck Unit, Macmillan Cancer Centre, University College London Hospital, London, UK.|Department of Plastic and Reconstructive Surgery, Royal Free Hospital, London, UK.|Charles Wolfson Centre for Reconstructive Surgery, Royal Free Hospital, London, UK.
authors.forename: P E M
authors.initials: PE
authors.lastname: Butler
mesh_terms: D000273:Adipose Tissue / Q000637:transplantation*; D001696:Biomechanical Phenomena / Q000502:physiology; D005355:Fibrosis / Q000000981:diagnostic imaging / Q000628:therapy*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D011878:Radiotherapy / Q000009:adverse effects*; D012867:Skin / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D053773:Transforming Growth Factor beta1 / Q000502:physiology; D014182:Transplantation, Autologous; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D010982:Platelet-Derived Growth Factor; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha