Gingival-derived mesenchymal stem cell therapy regenerated the radiated salivary glands: functional and histological evidence in murine model.

BACKGROUND: Radiotherapy in head and neck cancer management causes degeneration of the salivary glands (SG). This study was designed to determine the potential of gingival mesenchymal stem cells (GMSCs) as a cell-based therapy to regenerate irradiated parotid SG tissues and restore their function using a murine model. METHODS: Cultured isolated cells from gingival tissues of 4 healthy guinea pigs at passage 3 were characterized as GMSCSs using flow cytometry for surface markers and multilineage differentiation capacity. Twenty-one Guinea pigs were equally divided into three groups: Group I/Test, received single local irradiation of 15 Gy to the head and neck field followed by intravenous injection of labeled GMSCs, Group II/Positive control, which received the same irradiation dose followed by injection of phosphate buffer solution (PBS), and Group III/Negative control, received (PBS) injection only. Body weight and salivary flow rate (SFR) were measured at baseline, 11 days, 8-, 13- and 16-weeks post-irradiation. At 16 weeks, parotid glands were harvested for assessment of gland weight and histological and immunohistochemical analysis. RESULTS: The injected GMSCs homed to degenerated glands, with subsequent restoration of the normal gland histological acinar and tubular structure associated with a significant increase in cell proliferation and reduction in apoptotic activity. Subsequently, a significant increase in body weight and SFR, as well as an increase in gland weight at 16 weeks in comparison with the irradiated non-treated group were observed. CONCLUSION: The study provided a new potential therapeutic strategy for the treatment of xerostomia by re-engineering radiated SG using GMSCs.

Evaluation of muco-adhesive tacrolimus patch on caspase-3 induced apoptosis in oral lichen planus: a randomized clinical trial.

BACKGROUND: The study compared the clinical effectiveness of topical Tacrolimus (TAC) in patches or gel with Triamcinolone acetonide (TRI) gel for erosive/atrophic oral lichen planus (OLP) and investigated the influence of these therapies on Caspase-3 expression as a marker of apoptosis. METHODS: Thirty patients were randomly assigned into three equal groups to receive either topical TAC 0.1% patch twice daily, topical TAC 0.1% gel, or topical TRI 0.1% gel four times daily for 8 weeks. Each patient's clinical score (CS), visual analogue scale (VAS), and total atrophic area (TAA) of the marker lesion were measured at baseline, 2, 4, and 8 weeks of treatment, as well as after 4 weeks of treatment free period. Caspase-3 expression and lymphocytic counts (LC) were assessed in pre- and post-treatment biopsied stained sections. RESULTS: TAC patch resulted in a higher reduction in CS [- 14.00 (15.54%)] and VAS [- 70.21 (15.82%)] followed by TAC gel then TRI gel within the first two weeks. The reduction in VAS and TAA were significantly higher in TAC groups compared to TRI gel, although the difference between TAC treatment was not significant and this was observed throughout the treatment and follow-up periods. Caspase-3 expression increased in connective tissue in all groups. It decreased significantly within the epithelium in both TAC groups but increased in TRI gel. (LC) were significantly lowered with the TAC patch compared to other groups. The percentage change in Caspase-3 epithelial expression was significantly correlated to the CS, TAA, and LC. CONCLUSION: Both TAC patch and gel significantly decreased pain and lesion size than TRI gel, with a significant reduction in Caspase-3 expression within the epithelium in comparison to the increase seen with TRI gel. The study protocol was registered at www. CLINICALTRIALS: gov (NCT05139667) on 01/12/2021.

Oropharyngeal and otorhinological changes in end stage renal patients undergoing hemodialysis.

BACKGROUND: The study aimed to assess oropharyngeal and otorhinolaryngological changes in end stage renal disease (ESRD) patients undergoing hemodialysis and correlate the findings to renal functions. MATERIAL AND METHODS: This case-control study compared oral and otorhinolaryngological findings in 85 patients with (ESRD) on maintenance hemodialysis to age and sex matched 85 healthy controls. Frequencies of findings were calculated and compared and correlation between biochemical and the oral health parameters in case group was determined using T-test, chi-square and Pearson correlation test (significance were set at P<0.05). RESULTS: The frequency of oral signs and mucosal symptoms were significantly higher among ESRD compared to healthy controls. Dry mouth (34.12%), bad odour (32.94%), increased tongue coating (50.59%) and pale mucosa (45.88%) were the most commonly reported. Otorhinolaryngological findings was higher in cases than in controls, with otomycosis (10.59%) and allergic rhinitis (5.88%) being the most frequent findings. Serum creatinine and blood urea mean levels were higher in ESRD patients with oral and otorhinolaryngological findings compared to those without findings. CONCLUSIONS: Oral and nasal manifestations in patients with ESRD on maintenance hemodialysis were significantly higher in comparison to healthy individuals and were related to their serum creatinine and blood urea mean levels. Key words:Chronic kidney disease, renal dialysis, Oral manifestation, nasal, case control, Egypt.

Regenerative potential of cultured gingival fibroblasts in treatment of periodontal intrabony defects (randomized clinical and biochemical trial).

BACKGROUND: Defective cellular elements constitute an important challenge to achieve predictable periodontal regeneration. In an attempt to improve the cellularity of periodontal defects, gingival fibroblasts were implanted without their associated extracellular elements in periodontal defects to expose them to periodontal tissue mediators. In order to investigate the regenerative potential of gingival fibroblasts translocated into periodontal defects, the present study was designed to clinically and biochemically investigate the use of gingival fibroblasts (GF) and their associated mesenchymal stem cells (GMSC) in the treatment of intrabony periodontal defects. METHODS: A total of 20 subjects were randomly divided into two groups (n = 20). Group I: ten patients were included with ten intrabony periodontal defects that received ß-calcium triphosphate (ß-TCP) followed by collagen membrane defect coverage, while group II: (10 patients) ten periodontal defects received cultured gingival fibroblasts (GF) on the ß-TCP scaffold and covered by a collagen membrane. The clinical evaluation was carried out at the beginning and at 6 months. Gingival crevicular fluid (GCF) samples were collected directly from the test sites for the quantitative measurement of PDGF-BB and BMP-2 using the ELISA kit at 1, 7, 14, and 21 days after surgery. RESULTS: Group II reported a significantly greater reduction in vertical pocket depth (VPD) and CAL gain compared with group I after 6 months. Radiographic bone gain was statistically higher in group II compared with group I. A significantly higher concentration of PDGF-BB was observed in group II on days 1, 3, and 7 compared with group I. CONCLUSIONS: Translocation of gingival fibroblasts from gingival tissue to periodontal defects could be a promising option that increases cellular elements with regeneration potential. The concept of total isolation of gingival fibroblasts using occlusive membranes must be re-evaluated.

Topical pimecrolimus versus betamethasone for oral lichen planus: a randomized clinical trial.

OBJECTIVES: Oral lichen plans (OLP) is a potentially malignant inflammatory mucocutaneous disease. CD133 is an investigated surface marker for cancer stem-like cells (CSCs) that may be involved in tumor initiation in head and neck carcinomas. We compared short-term clinical effectiveness of topical pimecrolimus as selective inflammatory cytokine release inhibitor with betamethasone cream for erosive/atrophic OLP and investigated the influence of this therapy on CD133 expression. MATERIAL AND METHODS: Thirty patients were randomly assigned into two equal groups to receive topical pimecrolimus (group I) or betamethasone (group II) four times daily for 4 weeks. A marker lesion in each patient were assessed at baseline using clinical score (CS) and visual analog scale (VAS) then at 1, 2, and 4 weeks and after 4 weeks of treatment-free period. CD133 expression was detected in pre- and post-treatment immunostained sections. RESULTS: Both drugs showed a reduction in CS, VAS, and CD133 expressions after treatment termination (p < 0.001). Pimecrolimus-treated lesions showed significant higher 1st week reduction in severity (33.1% (22.2)), pain score (57.53% (14.27)), less recurrence in follow-up period and less CD133 expression by the end of the 1st 4 weeks compared with betamethasone. CONCLUSION: Pimecrolimus showed earlier clinical response and less recurrence rate compared with standard topical corticosteroid in symptomatic OLP lesions, and both treatment reduced CD133-positive CSC population. CLINICAL RELEVANCE: The study proved the benefits of topical pimecrolimus in early management of painful lesions of OLP and its ability to inhibit CSCs, suggesting a possible role in reducing risk of malignant transformation.