Human Salivary Gland Stem Cells Functionally Restore Radiation Damaged Salivary Glands

Author:

Pringle Sarah12,Maimets Martti12,van der Zwaag Marianne1,Stokman Monique A.23,van Gosliga Djoke12,Zwart Erik4,Witjes Max J.H.3,de Haan Gerald4,van Os Ronald4,Coppes Rob P.12

Affiliation:

1. Department of Cell Biology, University of Groningen, University Medical Centrum Groningen, Groningen, The Netherlands

2. Department of Radiation Oncology, University of Groningen, University Medical Centrum Groningen, Groningen, The Netherlands

3. Department of Oral & Maxillofacial Surgery, University of Groningen, University Medical Centrum Groningen, Groningen, The Netherlands

4. Laboratory of Ageing Biology and Stem Cells, European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

Abstract

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.

Funder

Netherlands Organisation for Health Research and Development

Netherlands Institute for Regenerative Medicine

Dutch Cancer Society

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

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