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The Wnt pathways have been shown to be critical for the fate of mesenchymal stem cells (MSCs) in vitro, but their roles in MSCs in vivo remain poorly characterized due to the lack of stable alterations in their signaling. In the present study, we constructed long-term and stable mMSCs lines with activated and inactivated β-catenin (the key molecule of the canonical Wnt signaling pathway) or ROR2 (the key molecule of the noncanonical Wnt5a/ROR2 signaling pathway) modifications with lentiviral vectors. We found that the transduction efficiencies mediated by the lentiviral vectors were 92.61-97.04% and were maintained over 20 passages of mMSCs. Transfection by lentiviral vectors not only regulated the mRNA and protein expression of β-catenin or ROR2 but also regulated nuclear β-catenin accumulation or the Wnt5a/JNK and Wnt5a/PKC pathways belonging to the canonical Wnt and noncanonical Wnt5a/ROR2 pathways, respectively. β-Catenin or ROR2 gene overexpression promoted mMSC proliferation, migration and differentiation into osteoblasts, while inhibiting the adipogenic differentiation of mMSCs. In contrast, inactivation of the β-catenin or ROR2 genes resulted in the opposite effects. Therefore, these results confirm that lentiviral vector transduction can facilitate sustained and efficient gene modification of the Wnt pathway in mMSCs. This study provides a method to investigate the effects of the Wnt pathway on the fate of mMSCs in vivo and for the further improvement of MSC-based therapies. J. Cell. Physiol. 229: 791-800, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The differentiation of mesenchymal stem cells (MSCs) into type II alveolar epithelial (AT II) cells in vivo and in vitro, is critical for reepithelization and recovery in acute lung injury (ALI), but the mechanisms responsible for differentiation are unclear. In the present study, we investigated the role of the canonical wnt pathway in the differentiation of mouse bone marrow-derived MSCs (mMSCs) into AT II cells. Using a modified co-culture system with murine lung epithelial-12 (MLE-12) cells and small airway growth media (SAGM) to efficiently drive mMSCs differentiation, we found that GSK 3β and β-catenin in the canonical wnt pathway were up-regulated during differentiation. The levels of surfactant protein (SP) C, SPB, and SPD, the specific markers of AT II cells, correspondingly increased in mMSCs when Wnt3a or LiCl was added to the co-culture system to activate wnt/β-catenin signaling. The expression of these factors was depressed to some extent by inhibiting the pathway with the addition of DKK 1. The differentiation rate of mMSCs also depends on their abilities to accumulate and survive in inflammatory tissue. Our results suggested that the activation of wnt/β-catenin signaling promoted mMSCs migration towards ALI mouse-derived lung tissue in a Transwell assay, and ameliorated the cell death and the reduction of Bcl-2/Bax induced by H2O2, which simultaneously caused reduced GSK 3β and β-catenin in mMSCs. These data supports a potential mechanism for the differentiation of mMSCs into AT II cells involving canonical wnt pathway activation, which may be significant to their application in ALI. J. Cell. Physiol. 228: 1270-1283, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background and Aims: Biliary disease is one of the most common causes of acute pancreatitis in adults; however, this cause and outcome in children have rarely been described in the literature. Therefore, the present study was conducted to evaluate the role of biliary disease as a cause of acute pancreatitis in children. Methods: The present study included 56 children with acute pancreatitis, of which 16 (29%) cases were associated with biliary disease. The 16 cases consisted of four boys and 12 girls ranging in age from 2 to 13 years. The underlying causes of the biliary disease were evaluated, as well as its clinical presentations, management modalities, and outcomes. Results: The causes of biliary disease in the 16 children included choledochal cyst in seven, biliary sludge in six, gallstone in two, and anomalous pancreaticobiliary junction in one. Acute pancreatitis with biliary disease showed increased presentation of jaundice and abnormalities in a liver-function test. Therapeutic interventions were performed more frequently in acute pancreatitis associated with biliary disease. All seven children with choledochal cysts needed hepaticojejunostomy. Of eight children with biliary sludge or gallstones, five children remained free of and two suffered from repeated attacks of pancreatitis after endoscopic papillotomy. Mortality did not occur. Conclusion: The present study suggests that biliary disease can be one of the causes of acute pancreatitis in children and has the clinical characteristics of jaundice and/or abnormalities in a liver-function test. Appropriate therapeutic interventions should be considered as the treatment modality. [ABSTRACT FROM AUTHOR]