title: Enhanced tissue remodelling efficacy of adipose-derived mesenchymal stem cells using injectable matrices in radiation-damaged salivary gland model.
abstract: The present study was conducted to introduce the use of a delivery carrier for local transplantation of human adipose tissue-derived mesenchymal stem cells (AdMSCs) into the salivary gland (SG) and analyse its ability to enhance radioprotection of AdMSCs against irradiation (IR)-induced damage. An injectable porcine small intestinal submucosa (SIS) matrix was used as a cell delivery carrier, and human AdMSCs were contained within SIS hydrogel (AdMSC/SIS). After local injection into SGs of mice following local IR, morphological and functional changes were evaluated in the sham, vehicle [phosphate-buffered saline (PBS)], SIS, AdMSC and AdMSC/SIS groups. Local transplantation of AdMSC resulted in less fibrosis, regardless of the use of a carrier, but the AdMSC/SIS group showed more mucin-producing acini relative to those in the PBS group. Functional restoration of salivation capacity and salivary protein synthesis was achieved in AdMSC and AdMSC/SIS groups, with a greater tendency being observed in the AdMSC/SIS group. AdMSC treatment resulted in tissue remodelling with a greater number of salivary epithelial cells (AQP-5), SG progenitor cells (c-Kit), endothelial cells (CD31) and myoepithelial cells (α-SMA), among which endothelial and myoepithelial cells significantly increased in the AdMSC/SIS group relative to the AdMSC group. AdMSC treatment alleviated IR-induced cell death, and the anti-apoptotic and anti-oxidative effects of AdMSC were enhanced in the AdMSC/SIS group relative to the AdMSC group. These results suggest local transplantation of AdMSC improves tissue remodelling following radiation damage in SG tissue, and that use of a carrier enhances the protective effects of AdMSC-mediated cellular protection against IR via paracrine secretion. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Inha University School of Medicine, Incheon, Republic of Korea.
authors.forename: Jeong-Seok
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Inha University School of Medicine, Incheon, Republic of Korea.
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: An
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Inha University School of Medicine, Incheon, Republic of Korea.
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Shin
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Inha University School of Medicine, Incheon, Republic of Korea.
authors.forename: Young-Mo
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Inha University School of Medicine, Incheon, Republic of Korea.
authors.forename: Jae-Yol
authors.initials: JY
authors.lastname: Lim
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects; D005260:Female; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology; D007267:Injections; D007413:Intestinal Mucosa / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D008954:Models, Biological; D017382:Reactive Oxygen Species / Q000378:metabolism; D012469:Salivary Glands / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology / Q000528:radiation effects*; D013552:Swine
chemical_list: D017382:Reactive Oxygen Species; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate
keywords: adipose tissue-derived mesenchymal stem cells; local transplantation; radiation; regeneration; salivary gland; small intestinal submucosa gel