title: Bone marrow-derived mesenchymal stem cells migrate to healthy and damaged salivary glands following stem cell infusion.
abstract: Xerostomia is a severe side effect of radiation therapy in head and neck cancer patients. To date, no satisfactory treatment option has been established. Because mesenchymal stem cells (MSCs) have been identified as a potential treatment modality, we aimed to evaluate stem cell distribution following intravenous and intraglandular injections using a surgical model of salivary gland damage and to analyse the effects of MSC injections on the recruitment of immune cells. The submandibular gland ducts of rats were surgically ligated. Syngeneic adult MSCs were isolated, immortalised by simian virus 40 (SV40) large T antigen and characterized by flow cytometry. MSCs were injected intravenously and intraglandularly. After 1, 3 and 7 days, the organs of interest were analysed for stem cell recruitment. Inflammation was analysed by immunohistochemical staining. We were able to demonstrate that, after intravenous injection, MSCs were recruited to normal and damaged submandibular glands on days 1, 3 and 7. Unexpectedly, stem cells were recruited to ligated and non-ligated glands in a comparable manner. After intraglandular injection of MSCs into ligated glands, the presence of MSCs, leucocytes and macrophages was enhanced, compared to intravenous injection of stem cells. Our data suggest that injected MSCs were retained within the inflamed glands, could become activated and subsequently recruited leucocytes to the sites of tissue damage.
authors.affiliation: Department of Otorhinolaryngology, Ulm University Medical Center, Ulm, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Schwarz
authors.affiliation: Apceth, Munich, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Huss
authors.affiliation: Institute of Pharmaceutical Technology, University of Leipzig, Leipzig, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Schulz-Siegmund
authors.affiliation: Institute of Pharmaceutical Technology, University of Leipzig, Leipzig, Germany.
authors.forename: Breda
authors.initials: B
authors.lastname: Vogel
authors.affiliation: Department of Otorhinolaryngology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Brandau
authors.affiliation: Department of Otorhinolaryngology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Lang
authors.affiliation: Department of Otorhinolaryngology, Ulm University Medical Center, Ulm, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Rotter
mesh_terms: D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000276:immunology; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000502:physiology; D002472:Cell Transformation, Viral; D002999:Clone Cells / Q000502:physiology; D005434:Flow Cytometry; D007150:Immunohistochemistry; D015552:Injections, Intralesional; D007275:Injections, Intravenous; D007962:Leukocytes / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000473:pathology / Q000502:physiology*; D009336:Necrosis; D017208:Rats, Wistar; D018987:Salivary Ducts / Q000473:pathology; D012793:Sialadenitis / Q000473:pathology / Q000628:therapy; D013539:Simian virus 40 / Q000276:immunology; D013363:Submandibular Gland / Q000473:pathology*; D013364:Submandibular Gland Diseases / Q000473:pathology / Q000628:therapy*; D013997:Time Factors
chemical_list: D000952:Antigens, Polyomavirus Transforming