Immunomodulatory and Tissue-preserving Effects of Human Dental Follicle Stem Cells in a Rat Cecal Ligation and Perforation Sepsis Model.

BACKGROUND: Mesenchymal stem cells may be used for the treatment of sepsis. Dental follicle stem cells (DFSCs) are easily accessible but have not been studied in vivo or in clinical trials in sepsis models. AIM OF THE STUDY: We aim to elucidate DFSC effects on host immunological functions in a rat cecal ligation and perforation (CLP) sepsis model. METHODS: Adult male rats were categorized into group 1 (sham procedure SP), group 2 (SP + 1 × 106 DFSCs administered 0 h after SP), group 3 (CLP + saline), group 4 (CLP + 1 × 106 DFSCs administered 0 h after CLP), and group 5 (CLP + 1 × 106 DFSCs administered 4 h after CLP). Green fluorescent protein-labeled cells were used for imaging. Histopathological examination of ileal tissues was performed. RESULTS: A significant increase in the percentage of CD4+/CD25+/Foxp3+ Treg cells in groups 4 and 5 occurred compared with that in group 3. No significant changes in CD3+/CD4+ helper T-cells and CD3+/CD8+ cytotoxic T-cells were observed. Treatment with DFSCs at 4 h significantly decreased the level of TNF-α compared with that in group 3. No significant changes in IL-10 levels and lymphocyte proliferation suppression were observed. During histopathological examination, no high scoring (Chiu scores: 3 or 4) rats were observed in the curative treatment group (group 5). CONCLUSIONS: Treatment with DFSC after 4 h of sepsis induction downregulates tissue inflammatory responses by decreasing TNF-α levels and increasing Treg cell ratio. This also has a protective effect on intestinal tissues during sepsis.

Quantitative assessment of liver fibrosis by digital image analysis: Relationship to Ishak staging and elasticity by shear-wave elastography.

OBJECTIVE: To analyze the relationship between fibrosis staged by Ishak stage and quantified by digital image analysis (DIA), and to reveal the optimum performance of shear-wave elastography (SWE) using quantitative DIA measurements as a comparative histological standard. METHODS: The proportionate area (PA) of fibrosis was measured by DIA from images of the PA of trichrome-stain (TPA) of 168 chronic hepatitis patients. SWE was performed in 105 patients. The accuracy of SWE for predicting the fibrosis defined by quantitative PA thresholds (≥ 2.5%, ≥ 5%, ≥ 10% and ≥ 20%, respectively) and by Ishak stages was measured using the area under the receiver operating characteristic curve (AUROC). RESULTS: DIA was proven to be highly reproducible (interclass correlation coefficient 0.926). The TPA range corresponding to each Ishak stage was large, widened as stages progressed, and reached its greatest extent in cirrhosis. TPA magnified at ×50 ranges 11.9-56% for Ishak stage F5-6. A good correlation between TPA and elasticity was presented for more advanced fibrosis (TPA ≥10%, rs = 0.732, P = 0.000) than milder fibrosis (TPA <10%, rs = 0.308, P = 0.006). With the advance of fibrosis either by stages or PA thresholds the discriminative accuracy of SWE gradually increased, but was less satisfactory for milder fibrosis. CONCLUSIONS: DIA may serve as a reproducible and reliable quantitative standard for surrogate tests for liver fibrosis. The performance and correlation of SWE with the fibrotic extent were better for advanced fibrosis, but less satisfactory for milder fibrosis.