[Effect of lipopolysaccharide-stimulated exosomes from human dental pulp stem cells combined with stromal cell-derived factor-1 on dental pulp regeneration].

Objective: To investigate the effect of exosomes from mild-inflammation- stimulated human dental pulp stem cells (hDPSC) combined with stromal cell-derived factor-1 (SDF-1) on dental pulp regeneration in rats. Methods: Primary hDPSCs were isolated, cultured and then stimulated by using lipopolysaccharide (LPS). The exosomes from the hDPSCs with (L-EXO) or without (N-EXO) LPS were extracted by overspeed differential centrifugation and were identified by transmission electron microscopy and Western blotting. Forty SD rats, aged 6-8 weeks, were equally divided into S group (SDF-1 alone), L+S group (L-EXO combined with SDF-1), N+S group (N-EXO combined with SDF-1) and blank control group (no substance implanted into the root canal) by random number table method. Bilateral mandibular first molars were used as the experimental teeth to establish pulpless root canal models and different contents were implanted into the root canals according to the groups. All rats were over-anesthetized and sacrificed at the 30th day after content implantation. Bilateral mandibular tissues were taken for histological evaluation by means of HE, Masson and immunohistochemical stainings. Results: The HE staining showed new pulp-like tissue in the root canals of all three experimental groups. The amount of new tissues and the number of cells in the tissues were greatest in L+S group and least in S group. Masson staining showed that the mineralized tissue in L+S group was arranged longitudinally along the root canal wall and the collagen fibers were arranged in an orderly fashion, while those in N+S group showed an irregular and disordered distribution. Quantitative analysis of the area of neovascularization in each group showed that the density of vessels in the L+S group [(2.03±0.65)%] was significantly higher than that in the S group [(0.65±0.05)%] and the N+S group [(1.06±0.38)%] respectively (F=5.879, P<0.05). Immunohistochemical staining showed that the expression of CXC chemokine receptor 4 (CXCR4) was significantly lower in S and L+S groups than in N+S group, with a statistically significant difference (F=8.633, P<0.01). Conclusions: Exosomes secreted by hDPSCs combined with SDF-1 might increase the amount of new tissue in the root canal and the density of blood vessels in the tissue. L-EXO showed a stronger effect than N-EXO did. The combination of L-EXO with SDF-1 might result in more regular arrangement of mineralized tissue and collagen fibers in the regenerative tissues.

Ascites in hepatitis C liver transplant recipients frequently occurs in the absence of advanced fibrosis.

Ascites after liver transplantation is uncommon (3-7%) but causes morbidity and mortality. Although hepatitis C (HCV), pretransplant ascites, encephalopathy and cold ischemia time have been identified as predictors, neither posttransplant renal function nor the severity of recurrent HCV (inflammatory grade; fibrosis stage) has been systematically assessed. Among 173 HCV transplants (1 January 1998 to 31 December 2002), 18 patients (10%) developed posttransplant ascites. Cox proportional hazards models identified recipient female gender (hazard ratio [HR]= 12.18; p = 0.0001), cold ischemia time (HR = 1.17 per incremental hour; p = 0.021) and posttransplant creatinine (Cr) (HR = 1.56 per incremental 1.0 mg/dL; p = 0.0052) as independent predictors. Ludwig-Batts inflammation grade (HR = 1.32; p = 0.36) and fibrosis stage (HR = 1.63; p = 0.12) were not significant predictors. The 18 recipients had 19 ascites episodes; 12/19 had fibrosis stage 0, 1 or 2 (10/12 with stage 0 or 1). All 12 lacked diagnostic parenchymal or vascular histopathology. Renal function at ascites diagnosis were similar for transplants with fibrosis stage 0, 1 or 2 versus 3 or 4 (1.8 +/- 1.6 vs. 1.6 +/- 0.6 mg/dL; Cr clearance 39.6 +/- 15.6 vs. 39.3 +/- 13.4 mL/min/1.73 m(2)). In conclusion, recipient female gender, cold ischemia time and poor posttransplant renal function were independent predictors of ascites after HCV liver transplantation. Two thirds of ascites episodes, however, occurred without significant fibrosis or histopathology.