Stress or injury induces cellular plasticity in salivary gland acinar cells

Mouth-Watering Results: Clinical Need, Current Approaches, and Future Directions for Salivary Gland Regeneration

“…Furthermore, whether the injured human SG can regenerate itself under adverse conditions remains unknown. Murine studies have provided evidence that, under severe injury, tissue-resident progenitor cells can undergo transdifferentiation [28,95,97]; however, whether this can occur in human SGs remains unanswered, but a report that human hepatocytes can transdifferentiate into biliary cells when transplanted into a mouse liver [145] provides encouraging evidence that cells of human origin can undergo transdifferentiation in vivo in response to injury. In conclusion, future studies demonstrating success of the above approaches in human trials will be pivotal in working toward a permanent cure for xerostomia.…”

“…While evidence demonstrates that, in the SMG, MIST1 + acinar cells replace themselves during homeostasis [90] and following IR [28], after severe injury (15 Gy IR), lineage tracing demonstrates that both KRT5 + and AXIN2 + cells are also able to replace acinar cells (confirmed by the markers aquaporin 5 [AQP5], MIST1, Na-K-Cl cotransporter, and inositol 1,4,5-triphosphate receptor 3) [28]. Conversely, stress and/or excessive inflammation is known to induce acinar-to-ductal metaplasia in the exocrine pancreas [94], and ductal ligation of the SMG results in reversible acinar cell atrophy and transient transdifferentiation of acinar cells to ductal cells [95], demonstrating a level of cellular plasticity in the SMG upon severe injury, although the mechanism by which this occurs is still unknown. There is evidence of transcription factor modulation resulting in plasticity, by cell-autonomously modulating gene expression in numerous secretory organs that lack regenerative potential under normal homeostatic conditions, such as the pancreas [96].…”

Immortalization of Salivary Gland Epithelial Cells of Xerostomic Patients: Establishment and Characterization of Novel Cell Lines

“…When salivary glands are damaged, acinar cells revert to a ductal-like state in mouse models [ 48 ]. Similar to the phenomenon observed in mice, rat acinar cells when extracted and cultured on plastic revert to a ductal like state, which can be reversed by inhibition of p-38 and/or Src pathways [ 16 , 17 ].…”

Salivary Gland Tissue Engineering Approaches: State of the Art and Future Directions

“…For example, the characteristics of secretory acinar cells, such as mucin biosynthesis [ 12 ] and amylase production [ 13 ], decrease significantly after 1 day in culture. Expression of Mist1 (bHLH15a), a transcription factor necessary to specify the acinar cell phenotype [ 14 ], drops significantly as well [ 15 , 16 ]. Thus, tissue engineering approaches have been leveraged to address the requirement of functional tissue to enable drug discovery and screening, regeneration, and fundamental studies.…”

“…For example, the characteristics of secretory acinar cells, such as mucin biosynthes [12] and amylase production [13], decrease significantly after 1 day in culture. Expressio of Mist1 (bHLH15a), a transcription factor necessary to specify the acinar cell phenotyp [14], drops significantly as well [15,16]. Thus, tissue engineering approaches have bee leveraged to address the requirement of functional tissue to enable drug discovery an The normal function of the salivary glands can be diminished by several conditions, such as off-target damage from radiation treatment for head or neck cancer, the autoimmune disease, Sjögren's syndrome, some systemic conditions including diabetes and neurological diseases, and a vast array of medications, including anti-hypertensives, β-blockers, antidepressants, and many others [2,6,7].…”