title: Contribution of INTRAMUSCULAR Autologous Adipose Tissue-Derived Stem Cell Injections to Treat Cutaneous Radiation Syndrome: Preliminary Results.
abstract: Cutaneous radiation syndrome caused by high dose located irradiation is characterized by delayed symptoms, incomplete wound healing, and poor revascularization. Subcutaneous adipose tissue derived stromal/stem cells have been shown to improve skin repair in a minipig model of cutaneous radiation syndrome despite a subcutaneous defect being a consequence of radio-induced muscular fibrosis. Based on the pro-myogenic potential of stromal/stem cells, a new protocol combining subcutaneous and intramuscular injections was evaluated in a preliminary study. Six female minipigs were locally irradiated at the dose of 50 Gy using a Co source (0.6 Gy min) and randomly divided into two groups. Three animals received the vehicle (phosphate-buffer-saline solution) and three animals received three injections of 75 × 10 adipose tissue derived stromal/stem cells each time (day 25, 46, and 66 post-irradiation). Pigs were euthanized on day 76 post-irradiation before development of clinical skin symptoms. All minipigs exhibited a homogeneous skin evolution. Macroscopic observation of irradiated muscles showed prominent fibrosis and necrosis areas in controls as opposed to adipose tissue-derived stromal/stem cells injected animals. Moreover, muscle biopsy analysis highlighted a recruitment of myofibroblasts (Immune Reactive Score: p < 0.01), an interleukin 10 secretion and a muscle regeneration pathway activation after intramuscular injections of adipose tissue-derived stromal/stem cells (western-blot: respectively, 200-fold change difference and twofold higher in treated animals). Globally, these preliminary data suggest that intramuscular injections of adipose tissue-derived stromal/stem cells improve muscle regeneration in the cutaneous-radiation syndrome. Further work is ongoing to evaluate this therapeutic strategy on a larger animal number with a longer clinical follow-up.
authors.affiliation: *Institut de Recherche Biomédicale des Armées (IRBA), Département des Effets Biologiques des Rayonnements, BP 73, Brétigny sur Orge Cedex, France; †Clinatec, 17 rue des Martyrs 38054, Grenoble cedex, France; ‡Institut für Radiobiologie der Bundeswehr, Neuherbergstraße 11, 80937 München, Germany.
authors.forename: Diane
authors.initials: D
authors.lastname: Riccobono
authors.forename: Diane
authors.initials: D
authors.lastname: Agay
authors.forename: Sabine
authors.initials: S
authors.lastname: François
authors.forename: Harry
authors.initials: H
authors.lastname: Scherthan
authors.forename: Michel
authors.initials: M
authors.lastname: Drouet
authors.forename: Fabien
authors.initials: F
authors.lastname: Forcheron
mesh_terms: D054508:Acute Radiation Syndrome / Q000473:pathology*; D017667:Adipocytes / Q000166:cytology; D000818:Animals; D002454:Cell Differentiation; D005260:Female; D007273:Injections, Intramuscular; D010865:Pilot Projects; D012867:Skin / Q000473:pathology* / Q000528:radiation effects*; D012871:Skin Diseases / Q000473:pathology* / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology; D013552:Swine; D013556:Swine, Miniature; D016896:Treatment Outcome