Gingival margin-derived stem/progenitor cells show significant periodontal regenerative potential.

No abstract

With the increasing information on the number, quality, and characteristics of hematopoietic stem cells (HSC) in umbilical cord and placental blood, this material has been found to be efficacious as an alternative source of HSC for transplantation in children. In this study, we sought to define the optimal conditions for ex vivo expansion of cord blood (CB) stem cells. These conditions include: the combinations and concentrations of hematopoietic growth factors (stem cell factor [SCF], granulocyte-macrophage colony-stimulating factor [GM-CSF], interleukin [IL]-3, thrombopoietin [Tpo], IL-6 and Fms-like tyrosine kinase 3 ligand [Flt-3L]), the duration of culture, and the effect of serum supplementation. In this study, 2 protocols were applied for ex vivo expansion of CB stem cells. In protocol I, 20 CB samples were expanded in a static, serum-added, liquid culture for 7 and 11 days using 5 cytokine cocktails. In protocol II, 10 CB samples were expanded for 7 days using cytokines of cocktail 1, with and without IL-6 and Flt-3L, in serum-added and serum-free culture media. This protocol was intended to verify the effect of IL-6, Flt-3L, and the role of serum supplementation in short-term liquid culture. From the present study, it can be concluded that cocktail 1 is the cocktail of choice for ex vivo expansion of CB stem cells in serum-free, liquid culture expanded for 7 days. We can also conclude that culture expanded for 7 days is better than 11 days, as the fold expansion of CD34+ cells was not significantly increased or even decreased in some of the cocktails used. Moreover, the percent of CD95+ cells (apoptotic cells) was significantly increased on day 11 compared to day 7 in the cocktails tested.

RBP7 is a member of the cellular retinol-binding protein (CRBP) family and previous data suggested a link between CRBPs and the malignant transformation of colon cancer cells. Here, we investigated the potential of RBP7 as a predictive biomarker for patients with colon cancer and determined its functional relevance for tumor progression. We analyzed RBP7 protein and mRNA expression in independent tissue collections of colon cancers with recorded follow-up data, including data from TCGA. We used gene set enrichment analyses to characterize its functional role. Effects of RBP7 on migration and invasion were determined in transwell assays. High expression of RBP7 was an independent biomarker of poor cancer specific survival in early and late stage colon cancer, and linked to colon cancer progression. Gene set enrichment analysis revealed a strong association of RBP7, colon cancer invasion and epithelial mesenchymal transition (EMT). Ectopic expression of RBP7 increased migration and invasion of colon cancer cells. Our findings demonstrate that RBP7 is a strong prognostic biomarker in colon cancer that functionally contributes to the malignant phenotype of colon cancer cells. This may aid in risk stratification for the therapeutic management of patients with colorectal cancer.

Signaling pathways that drive bladder cancer (BC) progression may be promising and specific targets for systemic therapy. Here, we investigated the clinical significance and targetability of NOTCH and mitogen‐activated protein kinase (MAPK) signaling for this aggressive malignancy. We assessed NOTCH1 and MAPK activity in 222 stage III and IV BC specimens of patients that had undergone radical cystectomy, and tested for clinical associations including cancer‐specific and overall survival. We examined therapeutic effects of NOTCH and MAPK repression in a murine xenograft model of human bladder cancer cells and evaluated tumor growth and tumor cell plasticity. In BC, NOTCH1 and MAPK signaling marked two distinct tumor cell subpopulations. The combination of high NOTCH1 and high MAPK activity indicated poor cancer‐specific and overall survival in univariate and multivariate analyses. Inhibition of NOTCH and MAPK in BC xenografts in vivo depleted targeted tumor cell subpopulations and revealed strong plasticity in signaling pathway activity. Combinatorial inhibition of NOTCH and MAPK signaling most strongly suppressed tumor growth. Our findings indicate that tumor cell subpopulations with high NOTCH and MAPK activity both contribute to tumor progression. Furthermore, we propose a new concept for BC therapy, which advocates specific and simultaneous targeting of these different tumor cell subpopulations through combined NOTCH and MAPK inhibition.