title: Purification and ex vivo expansion of fully functional salivary gland stem cells.
abstract: Hyposalivation often leads to irreversible and untreatable xerostomia. Salivary gland (SG) stem cell therapy is an attractive putative option to salvage these patients but is impeded by the limited availability of adult human tissue. Here, using murine SG cells, we demonstrate single-cell self-renewal, differentiation, enrichment of SG stem cells, and robust in vitro expansion. Dependent on stem cell marker expression, SG sphere-derived single cells could be differentiated in vitro into distinct lobular or ductal/lobular organoids, suggestive of progenitor or stem cell potency. Expanded cells were able to form miniglands/organoids containing multiple SG cell lineages. Expansion of these multipotent cells through serial passaging resulted in selection of a cell population, homogenous for stem cell marker expression (CD24(hi)/CD29(hi)). Cells highly expressing CD24 and CD29 could be prospectively isolated and were able to efficiently restore radiation-damaged SG function. Our approach will facilitate the use of adult SG stem cells for a variety of scientific and therapeutic purposes.
authors.affiliation: Department of Cell Biology, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713AV Groningen, the Netherlands.
authors.forename: Lalitha S Y
authors.initials: LS
authors.lastname: Nanduri
authors.affiliation: Department of Cell Biology, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713AV Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ Groningen, the Netherlands.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Baanstra
authors.affiliation: Department of Cell Biology, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713AV Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ Groningen, the Netherlands.
authors.forename: Hette
authors.initials: H
authors.lastname: Faber
authors.affiliation: Department of Cell Biology, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713AV Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ Groningen, the Netherlands.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Rocchi
authors.affiliation: Laboratory of Ageing Biology and Stem Cells, European Research Institute for the Biology of Aging (ERIBA), University Medical Center Groningen, University of Groningen, Building 3226, Antonius Deusinglaan 1, 9713AV Groningen, the Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Zwart
authors.affiliation: Laboratory of Ageing Biology and Stem Cells, European Research Institute for the Biology of Aging (ERIBA), University Medical Center Groningen, University of Groningen, Building 3226, Antonius Deusinglaan 1, 9713AV 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 Aging (ERIBA), University Medical Center Groningen, University of Groningen, Building 3226, Antonius Deusinglaan 1, 9713AV Groningen, the Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: van Os
authors.affiliation: Department of Cell Biology, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713AV Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ Groningen, the Netherlands. Electronic address: r.p.coppes@umcg.nl.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Coppes
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D019070:Cell Lineage; D002469:Cell Separation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016130:Immunophenotyping; D051379:Mice; D012469:Salivary Glands / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D059467:Transcriptome