Purification and Ex vivo expansion of fully functional salivary gland stem cells

Lalitha S.Y. Nanduri; Mirjam Baanstra; Hette Faber; Cecilia Rocchi; Erik Zwart; Gerald De Haan; Ronald Van Os; Robert P. Coppes

doi:10.1016/j.stemcr.2014.09.015

Purification and Ex vivo expansion of fully functional salivary gland stem cells

Lalitha S.Y. Nanduri, Mirjam Baanstra, Hette Faber, Cecilia Rocchi, Erik Zwart, Gerald De Haan, Ronald Van Os, Robert P. Coppes

Research output: Contribution to journal › Article › peer-review

133 Scopus citations

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.

Original language	English (US)
Pages (from-to)	957-964
Number of pages	8
Journal	Stem Cell Reports
Volume	3
Issue number	6
DOIs	https://doi.org/10.1016/j.stemcr.2014.09.015
State	Published - Dec 9 2014
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Genetics
Developmental Biology
Cell Biology

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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 (CD24hi/CD29hi). 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.",

author = "Nanduri, {Lalitha S.Y.} and Mirjam Baanstra and Hette Faber and Cecilia Rocchi and Erik Zwart and {De Haan}, Gerald and {Van Os}, Ronald and Coppes, {Robert P.}",

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AU - Nanduri, Lalitha S.Y.

AU - Baanstra, Mirjam

AU - Faber, Hette

AU - Rocchi, Cecilia

AU - Zwart, Erik

AU - De Haan, Gerald

AU - Van Os, Ronald

AU - Coppes, Robert P.

PY - 2014/12/9

Y1 - 2014/12/9

N2 - 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 (CD24hi/CD29hi). 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.

AB - 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 (CD24hi/CD29hi). 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.

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Purification and Ex vivo expansion of fully functional salivary gland stem cells

Abstract

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