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Radiation therapy for head and neck cancer damages local stem cells and epithelial cells in salivary glands (SG), leading to irreversible SG dysfunction. Biological understanding of the responses of tissue-resident stem cells to gravity is required to develop therapeutic strategies for damaged tissue regeneration. In this study, we successfully isolated human minor salivary gland stem cells (huMSGSCs), which have high proliferation rates, express multiple stem markers, and can be differentiated into mesenchymal cell types. Cell proliferation, sphere-forming ability, stemness marker expressions, and epithelial differentiation potentials were checked after exposing huMSGSCs short-term to hypergravity (HyperG) or microgravity (MicroG). Proliferation after exposure to HyperG (40 G ) was greater than exposure to 1G, but no difference was observed between MicroG (10− 3 G) and 1G. Numbers of large spheres were significantly higher post-HyperG and lower post-MicroG than at 1G, whereas numbers of small spheres were significantly lower post-HyperG and higher post-MicroG. The expressions of stemness markers (CD90, LGR5, CD29, and CD24) and junction markers (ZO-1 and ZO-2) were increased post-HyperG. Furthermore, increases in PAS staining and the gene expressions of albumin and CK19 confirmed that HyperG enhances the epithelial differentiation potential of huMSGSCs. This study shows that cultivating huMSGSCs under HyperG conditions enhances stemness and that a gravity control system could be applied to modulate huMSGSC functions.

Radioiodine (RI) treatment is widely used in patients with differentiated thyroid cancer. However, RI exposure often induces salivary gland (SG) dysfunction. In this study, we investigated the effect of curcumin on RI-induced SG dysfunction in mice. Mice were assigned to one of four groups (n = 6 per group) as follows: normal control, RI only, RI + curcumin, and RI + amifostine group. Salivary flow rate, lag time, and changes in 99m Tc (technetium)-pertechnetate uptake and excretion were measured, and changes in SG morphology and histology were analysed. Salivary epidermal growth factor content, amylase, and superoxide dismutase (SOD) activities were also measured. A terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was performed to assess SG apoptosis, and the expression of apoptosis-related protein was determined by western blotting. The reduced salivary flow rate and prolonged lag time in the RI group was restored by treatment with curcumin or amifostine. In the histological analysis, compared with the RI group, RI + curcumin and RI + amifostine groups had more mucin-rich acini and less periductal fibrosis. Compared with the RI group, RI + curcumin and RI + amifostine groups showed evidence of tissue remodelling, with a greater number of salivary epithelial cells (AQP-5-positive), SG ductal cells (CK18-positive), endothelial cells (CD31-positive), and myoepithelial cells (α-SMA-positive). RI + curcumin and RI + amifostine groups alleviated RI-induced cell death, demonstrating antiapoptotic effect, compared with the RI group. Both SOD activity and the protein expression levels of SOD2 were higher in the RI + curcumin and RI + amifostine groups than in the RI group. Our results demonstrate that curcumin ameliorates RI-induced SG dysfunction in mice.

Background We examined the regenerative efficacy of the activated platelet-rich plasma (PRP) concentrate administered by local injection in an animal model mimicking partial glossectomy for tongue cancer. Methods Four-week-old mice were randomized to four groups; (1) a treatment-naive control group, (2) a PRP group, (3) a hemiglossectomy group, and (4) a hemiglossectomy + PRP group. The activated PRP concentrate was injected into the deep layer of resected surfaces of mouse tongues immediately after excision, and tongue widths and lengths were measured on postoperative days (POD) 5 and 12. Gross tongue morphologies and microscopic findings were investigated. Inflammation and fibrous tissue areas were also measured, and immunohistochemical analysis was performed for c-kit, neurofilament, and S-100. Results The activated PRP concentrate reduced wound scar contracture, promoted wound healing, and reduced inflammation and wound fibrosis. On POD 12, histologic findings in the hemiglossectomy + PRP group were similar to those in the normal control group, and the intensity of stem cell factor receptor c-kit expression was also significantly greater in the PRP group than in the hemiglossectomy group on POD 12. Immunohistochemical staining revealed S100 and neurofilament expressions in the hemiglossectomy + PRP group were significantly more intense than in the hemiglossectomy group. Conclusion Intralesional activated PRP concentrate injection has potential use for tongue regeneration, wound healing, and neural regeneration with minimal scarring after partial glossectomy.

After radioiodine (RI) therapy, patients with thyroid cancer frequently suffer from painful salivary gland (SG) swelling, xerostomia, taste alterations, and oral infections. This study was aimed to determine whether adipose-derived mesenchymal stem cells (AdMSCs) might restore RI-induced SG dysfunction in a murine model. Forty -five mice were divided into three groups; a PBS sham group, a RI+ PBS sham group (0.01 mCi/g mouse, orally), and an RI+AdMSCs (1 × 105 cells/150 uL, intraglandular injection on experimental day 28) treated group. At 16 weeks after RI treatment, body weights, SG weight, salivary flow rates (SFRs), and salivary lag times were measured. Morphologic and histologic examinations and immunohistochemistry (IHC) were performed and the activities of amylase and EGF in saliva were also measured. Changes in salivary 99mTc pertechnetate excretion were followed by SPECT and TUNEL assays were performed. The body and SG weights were similar in the AdMSCs and sham groups. Hematoxylin and eosin staining revealed the AdMSCs group had more mucin-containing acini than the RI group. Furthermore, AdMSCs treatment resulted in tissue remodeling and elevated expressions of epithelial (AQP5) and endothelial (CD31) markers, and increased SFRs. The activities of amylase and EGF were higher in the AdMSCs group than in the RI treated group. 99mTc pertechnetate excretions were similar in the AdMSCs and sham group. Also, TUNEL positive apoptotic cell numbers were less in the AdMSCs group than in the RI group. Local delivery of AdMSCs might regenerate SG damage induced by RI.

Objectives This study was conducted to investigate the dose-response characteristics of radioiodine on salivary glands and to investigate the mechanism responsible for radioiodine-induced salivary glands toxicity. Methods Twenty-four mice were divided into six groups: 0, 0.05, 0.10, 0.20, 0.40, and 0.80 mCi/20 g mouse, administered orally. Mortalities were noted 12 months after radioiodine administration. Body weights, gland weights, salivary lag times, flow rates, and changes in 99m Tc pertechnetate were recorded. Histopathological changes and mRNA expressions were also evaluated, and immunohistochemical analysis and apoptotic assays were performed. Results Survival rates, body weights, gland weights, and flow rates decreased, and lag times increased on increasing radioiodine dose. Animals administered radioiodine showed acinar atrophy, striated duct dilations, and lymphocytic infiltration in glands and irregular destruction of epithelial surfaces of tongue. The uptake and excretion of 99m Tc pertechnetate were impaired by radioiodine. Immunohistochemical analysis showed that numbers of salivary epithelial, myoepithelial, and endothelial cells decreased and that numbers of ductal cells increased with radioiodine dose. Oxidative stress biomarker levels increased; reactive oxygen species scavenger levels decreased; and numbers of apoptotic cells increased in animals exposed to higher radioiodine doses. Conclusion These dose-related, long-term effects on salivary gland should be taken into account when determining radioiodine doses. Level of evidence NA Laryngoscope, 130:2173-2178, 2020.

Nanocellulose has emerged for a wide range of applications in biomedical engineering because of its water absorption capacity, appropriate elasticity. We investigated the hemostatic and regenerative abilities of an expanding polyvinyl alcohol (PVA)-nanocellulose sponge on nasal mucosal defects. A 3 mm-diameter nasal defect was made in experimental rabbits. Rabbits were divided into four groups with control, vaseline, PVA and PVA-nanocellulose packing groups. After the defect was created, bleeding times and amounts were monitored. Packing materials were removed on experimental day (ED) 2. On ED 3, 7 and 14, histological analysis and immunohistochemical study for neutrophils were performed. Inflammatory cells were counted and epithelial thicknesses were evaluated. Bleeding amounts and times in the vaseline packing group were smaller than in the PVA groups. PVA-nanocellulose group showed less neutrophils than in the other groups on ED 7. Average epithelium thickness in the PVA-nanocellulose group was significantly smaller than in the control group at ED 7, but at ED 14, there was no significant intergroup difference. PVA-nanocellulose group had a significant lower inflammatory cell count than the control group on ED 7. PVA-nanocellulose sponge applied to nasal mucosal defects can significantly enhance mucosal regeneration during early wound healing.