title: Human Salivary Gland Stem Cells Functionally Restore Radiation Damaged Salivary Glands.
abstract: Adult stem cells are often touted as therapeutic agents in the regenerative medicine field, however data detailing both the engraftment and functional capabilities of solid tissue derived human adult epithelial stem cells is scarce. Here we show the isolation of adult human salivary gland (SG) stem/progenitor cells and demonstrate at the single cell level in vitro self-renewal and differentiation into multilineage organoids. We also show in vivo functionality, long-term engraftment, and functional restoration in a xenotransplantation model. Indeed, transplanted human salisphere-derived cells restored saliva production and greatly improved the regenerative potential of irradiated SGs. Further selection for c-Kit expression enriched for cells with enhanced regenerative potencies. Interestingly, interaction of transplanted cells with the recipient SG may also be involved in functional recovery. Thus, we show for the first time that salispheres cultured from human SGs contain stem/progenitor cells capable of self-renewal and differentiation and rescue of saliva production. Our study underpins the therapeutic promise of salisphere cell therapy for the treatment of xerostomia.
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Centrum Groningen, Groningen, The Netherlands.|Department of Radiation Oncology, University of Groningen, University Medical Centrum Groningen, Groningen, The Netherlands.
authors.forename: Sarah
authors.initials: S
authors.lastname: Pringle
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Centrum Groningen, Groningen, The Netherlands.|Department of Radiation Oncology, University of Groningen, University Medical Centrum Groningen, Groningen, The Netherlands.
authors.forename: Martti
authors.initials: M
authors.lastname: Maimets
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Centrum Groningen, Groningen, The Netherlands.
authors.forename: Marianne
authors.initials: M
authors.lastname: van der Zwaag
authors.affiliation: Department of Radiation Oncology, University of Groningen, University Medical Centrum Groningen, Groningen, The Netherlands.|Department of Oral & Maxillofacial Surgery, University of Groningen, University Medical Centrum Groningen, Groningen, The Netherlands.
authors.forename: Monique A
authors.initials: MA
authors.lastname: Stokman
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Centrum Groningen, Groningen, The Netherlands.|Department of Radiation Oncology, University of Groningen, University Medical Centrum Groningen, Groningen, The Netherlands.
authors.forename: Djoke
authors.initials: D
authors.lastname: van Gosliga
authors.affiliation: Laboratory of Ageing Biology and Stem Cells, European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Zwart
authors.affiliation: Department of Oral & Maxillofacial Surgery, University of Groningen, University Medical Centrum Groningen, Groningen, The Netherlands.
authors.forename: Max J H
authors.initials: MJ
authors.lastname: Witjes
authors.affiliation: Laboratory of Ageing Biology and Stem Cells, European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Gerald
authors.initials: G
authors.lastname: de Haan
authors.affiliation: Laboratory of Ageing Biology and Stem Cells, European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: van Os
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Centrum Groningen, Groningen, The Netherlands.|Department of Radiation Oncology, University of Groningen, University Medical Centrum Groningen, Groningen, The Netherlands.
authors.forename: Rob P
authors.initials: RP
authors.lastname: Coppes
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000528:radiation effects; D018507:Gene Expression Regulation, Developmental / Q000528:radiation effects; D006801:Humans; D051379:Mice; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis* / Q000235:genetics; D011827:Radiation; D012469:Salivary Glands / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D059010:Single-Cell Analysis; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D014987:Xerostomia / Q000473:pathology / Q000628:therapy*
chemical_list: D019009:Proto-Oncogene Proteins c-kit
keywords: Adult stem cells; Differentiation; Human salivary gland stem cells; Organoids; Radiation induced xerostomia