title: Tumor necrosis factor-α-activated human adipose tissue-derived mesenchymal stem cells accelerate cutaneous wound healing through paracrine mechanisms.
abstract: Human adipose tissue-derived mesenchymal stem cells (ASCs) stimulate regeneration of injured tissues by secretion of various cytokines and chemokines. Wound healing is mediated by multiple steps including inflammation, epithelialization, neoangiogenesis, and proliferation. To explore the paracrine functions of ASCs on regeneration of injured tissues, cells were treated with tumor necrosis factor-α (TNF-α), a key inflammatory cytokine, and the effects of TNF-α-conditioned medium (CM) on tissue regeneration were determined using a rat excisional wound model. We demonstrated that TNF-α CM accelerated wound closure, angiogenesis, proliferation, and infiltration of immune cells into the cutaneous wound in vivo. To assess the role of proinflammatory cytokines IL-6 and IL-8, which are included in TNF-α CM, IL-6 and IL-8 were depleted from TNF-α CM using immunoprecipitation. Depletion of IL-6 or IL-8 largely attenuated TNF-α CM-stimulated wound closure, angiogenesis, proliferation, and infiltration of immune cells. These results suggest that TNF-α-activated ASCs accelerate cutaneous wound healing through paracrine mechanisms involving IL-6 and IL-8.
authors: Medical Research Center for Ischemic Tissue Regeneration, The Medical Research Institute, School of Medicine, Pusan National University, Gyeongsangnam-do, Republic of Korea.
authors: Soon Chul
authors: SC
authors: Heo
authors: Eun Su
authors: ES
authors: Jeon
authors: Il Hwan
authors: IH
authors: Lee
authors: Hoon Soo
authors: HS
authors: Kim
authors: Moon Bum
authors: MB
authors: Kim
authors: Jae Ho
authors: JH
authors: Kim
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004848:Epithelium / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology; D016209:Interleukin-8 / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000098:blood supply / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014945:Wound Healing
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha