Human Salivary Gland Stem Cells Functionally Restore Radiation Damaged Salivary Glands

Sarah Pringle, Martti Maimets, Marianne van der Zwaag, Monique A Stokman, Djoke van Gosliga, Erik Zwart, Max J H Witjes, Gerald de Haan, Ronald van Os, Rob P Coppes

92 Citationer (Scopus)

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.

OriginalsprogEngelsk
TidsskriftStem Cells
Vol/bind34
Udgave nummer3
Sider (fra-til)640-52
Antal sider13
ISSN1066-5099
DOI
StatusUdgivet - 1 mar. 2016
Udgivet eksterntJa

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