Open AccessHuman Salivary Gland Stem Cells Functionally Restore Radiation Damaged Salivary Glands
Author(s) -
Pringle Sarah,
Maimets Martti,
van der Zwaag Marianne,
Stokman Monique A.,
van Gosliga Djoke,
Zwart Erik,
Witjes Max J.H.,
de Haan Gerald,
van Os Ronald,
Coppes Rob P.
Publication year - 2016
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2278
Subject(s) - biology , stem cell , progenitor cell , microbiology and biotechnology , regenerative medicine , adult stem cell , salivary gland , immunology , saliva , regeneration (biology) , xenotransplantation , cellular differentiation , organoid , in vitro , transplantation , endothelial stem cell , medicine , genetics , biochemistry , gene
A bstract 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. S tem C ells 2016;34:640–652