Background Bacterial vaginosis (BV) is a common imbalance of the vaginal microbiota characterized by overgrowth of diverse Actinobacteria, Firmicutes, and Gram-negative anaerobes. Women with BV are at increased risk of secondary reproductive tract infections and adverse pregnancy outcomes. However, which specific bacteria cause clinical features of BV is unclear. Methods We previously demonstrated that Gardnerella vaginalis could elicit many BV features in mice. In this study, we established a BV model in which we coinfected mice with G. vaginalis and another species commonly found in women with BV: Prevotella bivia. Results This coinfection model recapitulates several aspects of human BV, including vaginal sialidase activity (a diagnostic BV feature independently associated with adverse outcomes), epithelial exfoliation, and ascending infection. It is notable that G. vaginalis facilitated uterine infection by P. bivia. Conclusions Taken together, our model provides a framework for advancing our understanding of the role of individual or combinations of BV-associated bacteria in BV pathogenesis.

The effects of mesenchymal stem cells (MSC) on the growth and metastasis of human malignancies including hepatocellular carcinoma (HCC) are controversial, and the underlying mechanisms are not yet understood. The aim of this study was to explore the role of MSC in the progression of HCC. We investigated the effect of MSC on in vitro proliferation and invasion and in vivo tumor growth and pulmonary metastasis of MHCC97-H HCC cells with a high metastatic potential. The mRNA and protein levels of transforming growth factor-beta 1 (TGFb1) and MMP, and their association with the effects of MSC on HCC cells were also evaluated. Co-culture of MHCC97-H cells with MSC conditioned medium significantly enhanced in vitro proliferation but inhibited invasiveness. Following MSC treatment of a nude mouse model bearing human HCC, the MSC were predominantly located in the HCC tissues. Compared with controls, MSC-treated mice exhibited significantly larger tumors (3080.51 ± 1234.78 mm 3 vs 2223.75 ± 1000.60 mm 3 , P = 0.045), but decreased cellular numbers of lung metastases (49.75 ± 18.86 vs 227.22 ± 74.67, P = 0.046). Expression of TGFb1 and MMP-2 was significantly downregulated in the MSCtreated HCC cells. TGFb siRNA concurrently downregulated expression of TGFb and MMP-2 in HCC cells and blocked the MSC-induced proliferation and invasiveness of MHCC97-H cells. The MSC enhanced tumor growth but significantly inhibited the invasiveness and metastasis of HCC, possibly through downregulation of TGFb1. These findings suggest that MSC could be useful in controlling metastatic recurrence of HCC. (Cancer Sci 2010; 101: 2546-2553 H epatocellular carcinoma (HCC) is the third leading cause of cancer death in the world, and the second in China.(1,2)The extremely poor prognosis of HCC is largely due to the high rate of intra-hepatic metastases that develop through invasion of the portal vein and spread to other parts of the liver.(3,4) Therefore, exploring new therapeutic strategies to control the metastasis of HCC is the key issue for prolonging patient survival. Recently accumulated evidence indicating that bone marrow stem cells contribute to the development and progression of cancers might be helpful in the diagnosis and treatment of human cancers.(6-11) Bone marrow cells have also been found to be closely associated with liver diseases, and can indirectly influence hepatocarcinogenesis.(12) However, their significance with respect to HCC is far from fully understood.Mesenchymal stem cells (MSC) from adult bone marrow can be induced to differentiate into a variety of mesenchymal tissues both in vitro and in vivo.(13-15) They can even demonstrate sitespecific differentiation, and have unique immunological characteristics that allow persistence in a xenogeneic environment. (16) Therefore, MSC present an intriguing model in which to investigate the differentiation of stem cells, as well as cell and gene therapy applications. However, little is known about the functional contribution of MSC to tumor growth and progression, and the publish...

Abstract. Mesenchymal stem cells (MSCs) may influence the growth and metastasis of various human malignancies, including hepatocellular carcinoma (HCC). Therefore, the underlying mechanisms via which MSCs are able to affect malignancies require investigation. In the present study, the potential role of MSC in the angiogenesis of HCC was investigated. A total of 17 nude mouse models exhibiting human HCC were used to evaluate the effects of MSC on angiogenesis. A total of 8 mice were injected with human MSCs via the tail vein, and the remaining 9 mice were injected with phosphate-buffered saline as a control. A total of 35 days subsequent to the injection of MSCs, the microvessel density (MVD) of tumors was evaluated by immunostaining, using cluster of differentiation 31 antibody. The mRNA levels of transforming growth factor (TGF)β1, Smad2 and Smad7 were detected using reverse transcription-quantitative polymerase chain reaction. Protein