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.
| Original language | English |
|---|---|
| Journal | Stem Cells |
| Volume | 34 |
| Issue number | 3 |
| Pages (from-to) | 640-52 |
| Number of pages | 13 |
| ISSN | 1066-5099 |
| DOIs | |
| Publication status | Published - 1 Mar 2016 |
| Externally published | Yes |
Keywords
- Animals
- Cell Differentiation/genetics
- Gene Expression Regulation, Developmental/radiation effects
- Humans
- Mice
- Proto-Oncogene Proteins c-kit/biosynthesis
- Radiation
- Salivary Glands/cytology
- Single-Cell Analysis
- Stem Cell Transplantation
- Stem Cells/cytology
- Xerostomia/pathology
