Stress or injury induces cellular plasticity in salivary gland acinar cells

• Published in: Cell and tissue research 2020-06, Vol.380 (3), p.487-497
• Main Authors: Shubin, Andrew D., Sharipol, Azmeer, Felong, Timothy J., Weng, Pei-Lun, Schutrum, Brittany E., Joe, Debria S., Aure, Marit H., Benoit, Danielle S.W., Ovitt, Catherine E.
• Format: Article
• Language: English
• Subjects: Acinar cells; Acinar Cells - cytology; Acinar Cells - pathology; Animals; Basic Helix-Loop-Helix Transcription Factors - metabolism; Biomedical and Life Sciences; Biomedicine; Cell culture; Cell Plasticity; Cells, Cultured; Ethylenediaminetetraacetic acid; Head & neck cancer; Health aspects; Human Genetics; Hydrogels; Male; Mechanical properties; Mice; Mice, Inbred C57BL; Molecular Medicine; Phenotypes; Plasticity; Proteomics; Radiation therapy; Regeneration; Regular Article; Salivary gland; Sjogren's syndrome; Submandibular gland; Submandibular Gland - cytology; Submandibular Gland - injuries; Submandibular Gland - pathology; Xerostomia
• ISSN: 0302-766X; 1432-0878
• DOI: 10.1007/s00441-019-03157-w

Salivary gland function is severely disrupted by radiation therapy used to treat patients diagnosed with head and neck cancer and by Sjögren’s syndrome. The resulting condition, which results in xerostomia or dry mouth, is due to irreversible loss of the secretory acinar cells within the major salivary glands. There are presently no treatments for the resolution of xerostomia. Cell-based approaches could be employed to repopulate acinar cells in the salivary gland but investigations into potential therapeutic strategies are limited by the challenges of maintaining and expanding acinar cells in vitro. We investigate the encapsulation of salivary gland cell aggregates within PEG hydrogels as a means of culturing secretory acinar cells. Lineage tracing was used to monitor the fate of acinar cells isolated from murine submandibular gland (SMG). Upon initial formation in vitro, SMG aggregates comprise both acinar and duct cells, with the majority cells of acinar origin. With longer culture times, acinar cells significantly decreased the expression of specific markers and activated the expression of keratins normally found in duct cells. A similar acinar-to-duct cell transition was also observed in vivo, following duct ligation injury. These results indicate that under conditions of stress (mechanical and enzymatic isolation from glands) or injury (duct ligation), salivary gland acinar cells exhibit plasticity to adopt a duct cell phenotype.