Mesenchymal Stromal Cells Improve Salivary Function and Reduce Lymphocytic Infiltrates in Mice with Sjögren's-Like Disease

Non-obese diabetic (NOD) mice develop Sjögren's-like disease (SS-like) with loss of saliva flow and increased lymphocytic infiltrates in salivary glands (SGs). There are recent reports using multipotent mesenchymal stromal cells (MSCs) as a therapeutic strategy for autoimmune diseases due to their anti-inflammatory and immunomodulatory capabilities. This paper proposed a combined immuno- and cell-based therapy consisting of: A) an injection of complete Freund's adjuvant (CFA) to eradicate autoreactive T lymphocytes, and B) transplantations of MSCs to reselect lymphocytes. The objective of this was to test the effectiveness of CD45(-)/TER119(-) cells (MSCs) in re-establishing salivary function and in reducing the number of lymphocytic infiltrates (foci) in SGs. The second objective was to study if the mechanisms underlying a decrease in inflammation (focus score) was due to CFA, MSCs, or CFA+MSCs combined.Donor MSCs were isolated from bones of male transgenic eGFP mice. Eight week-old female NOD mice received one of the following treatments: insulin, CFA, MSC, or CFA+MSC (combined therapy). Mice were followed for 14 weeks post-therapy. CD45(-)/TER119(-) cells demonstrated characteristics of MSCs as they were positive for Sca-1, CD106, CD105, CD73, CD29, CD44, negative for CD45, TER119, CD11b, had high number of CFU-F, and differentiated into osteocytes, chondrocytes and adipocytes. Both MSC and MSC+CFA groups prevented loss of saliva flow and reduced lymphocytic infiltrations in SGs. Moreover, the influx of T and B cells decreased in all foci in MSC and MSC+CFA groups, while the frequency of Foxp3(+) (T(reg)) cell was increased. MSC-therapy alone reduced inflammation (TNF-α, TGF-β), but the combination of MSC+CFA reduced inflammation and increased the regenerative potential of SGs (FGF-2, EGF).The combined use of MSC+CFA was effective in both preventing saliva secretion loss and reducing lymphocytic influx in salivary glands

Antibiotic resistance in severe odontogenic infections of the South Australian population: a 9-year retrospective audit

Background: The aims of this study were to evaluate the microbiological trends in severe odontogenic infections requiring hospital admission in the South Australian Oral and Maxillofacial Surgery Unit. Rates of antibiotic resistance to empirical antibiotic regimens were determined to quantify the clinical implications of antibiotic‐resistant odontogenic infections. Methods: A retrospective case audit was performed on all odontogenic infections admitted to the Royal Adelaide Hospital over a 9‐year period. Data was collected regarding demographics, microbiological culture and sensitivity results, and clinical outcome variables. Results: Of a total of 672 patients, microbiology data was available for 447 cases. Penicillin‐resistant organisms were identified in 10.8% of patients, who required a significantly longer length of hospital admission (mean, 9.93 days) and higher rates of non‐response to initial surgical therapy (40%). Conclusions: There were moderate rates of antibiotic‐resistant odontogenic infections within the South Australian population. Patients within this subgroup demonstrate markedly poorer clinical outcomes. Effective treatment of odontogenic infections involves early operative intervention, with adjunctive use of appropriate antibiotic therapy that involves close monitoring of response to removal of the cause and use of first‐line antibiotic agents. Cases that fail to respond require urgent specialist review in order to reduce morbidity and mortality outcomes.I Liau, J Han, K Bayetto, B May, A Goss, P Sambrook, A Chen