title: Salisphere derived c-Kit+ cell transplantation restores tissue homeostasis in irradiated salivary gland.
abstract: BACKGROUND
  During radiotherapy salivary glands of head and neck cancer patients are unavoidably co-irradiated, potentially resulting in life-long impairment. Recently we showed that transplantation of salisphere-derived c-Kit expressing cells can functionally regenerate irradiated salivary glands. This study aims to select a more potent subpopulation of c-Kit(+) cells, co-expressing stem cell markers and to investigate whether long-term tissue homeostasis is restored after stem cell transplantation.
  
  
  RESULTS
  Salisphere derived c-Kit(+) cells that co-expressed CD24 and/or CD49f markers, were intra-glandularly injected into 15 Gy irradiated submandibular glands of mice. Particularly, c-Kit(+)/CD24(+)/CD49f(+) cell transplanted mice improved saliva production (54.59 ± 11.1%) versus the irradiated control group (21.5 ± 8.7%). Increase in expression of cells with differentiated duct cell markers like, cytokeratins (CK8, 18, 7 and 14) indicated functional recovery of this compartment. Moreover, ductal stem cell marker expression like c-Kit, CD133, CD24 and CD49f reappeared after transplantation indicating long-term functional maintenance potential of the gland. Furthermore, a normalization of vascularization as indicated by CD31 expression and reduction of fibrosis was observed, indicative of normalization of the microenvironment.
  
  
  CONCLUSIONS
  Our results show that stem cell transplantation not only rescues hypo-salivation, but also restores tissue homeostasis of the irradiated gland, necessary for long-term maintenance of adult tissue.
authors.affiliation: Department of Cell Biology, University Medical Center Groningen, The Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Lalitha S Y
authors.initials: LS
authors.lastname: Nanduri
authors.forename: Isabelle M A
authors.initials: IM
authors.lastname: Lombaert
authors.forename: Marianne
authors.initials: M
authors.lastname: van der Zwaag
authors.forename: Hette
authors.initials: H
authors.lastname: Faber
authors.forename: Jeanette F
authors.initials: JF
authors.lastname: Brunsting
authors.forename: Ronald P
authors.initials: RP
authors.lastname: van Os
authors.forename: Robert P
authors.initials: RP
authors.lastname: Coppes
mesh_terms: D000818:Animals; D051927:CD24 Antigen / Q000032:analysis; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy; D006706:Homeostasis; D039503:Integrin alpha6 / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000502:physiology*; D011832:Radiation Injuries / Q000628:therapy*; D012038:Regeneration; D012469:Salivary Glands / Q000502:physiology / Q000528:radiation effects*; D033581:Stem Cell Transplantation
chemical_list: D051927:CD24 Antigen; C497890:Cd24a protein, mouse; D039503:Integrin alpha6; D019009:Proto-Oncogene Proteins c-kit
keywords: Regeneration; Salivary gland; Stem cell; Tissue homeostasis; c-Kit