Comparative Studies of Fibrin-Based Engineered Vascular Tissues and Notch Signaling from Progenitor Cells.

The main impetus of vascular tissue engineering is clinical translation, but an equally appealing and impactful use of engineered vascular tissues is as preclinical testing platforms for studying vascular disease and developing therapeutic drugs and understanding of physiologically relevant vascular biology. Developing model engineered tissues will aid in narrowing the significant knowledge gaps in functional tissue formation, which is regulated by intricate cell signaling in a three-dimensional space. In this study, we fabricated tubular engineered vascular tissues using cross-linked fibrinogen as a scaffold and nondifferentiated embryonic rat vascular smooth muscle cell line (A10 cells) and mouse embryonic multipotent mesenchymal progenitor cell line (10T1/2 cells) as model vascular cells.

The effects of progenitor and differentiated cells on ectopic calcification of engineered vascular tissues.

Ectopic vascular calcification associated with aging, diabetes mellitus, atherosclerosis, and chronic kidney disease is a considerable risk factor for cardiovascular events and death. Although vascular smooth muscle cells are primarily implicated in calcification, the role of progenitor cells is less known. In this study, we engineered tubular vascular tissues from embryonic multipotent mesenchymal progenitor cells either without differentiating or after differentiating them into smooth muscle cells and studied ectopic calcification through targeted gene analysis.

Emerging Strategies for Stem Cell Lineage Commitment in Tissue Engineering and Regenerative Medicine.

Stem cells have transformed the fields of tissue engineering and regenerative medicine, and their potential to further advance these fields cannot be overstated. The stem cell niche is a dynamic microenvironment that determines cell fate during development and tissue repair following an injury. Classically, stem cells were studied in isolation of their microenvironment; however, contemporary research has produced a myriad of evidence that shows the importance of multiple aspects of the stem cell niche in regulating their processes.

Monensin inhibits epidermal growth factor receptor trafficking and activation: synergistic cytotoxicity in combination with EGFR inhibitors.

Targeting the EGFR, with inhibitors such as erlotinib, represents a promising therapeutic option in advanced head and neck squamous cell carcinomas (HNSCC). However, they lack significant efficacy as single agents. Recently, we identified the ability of statins to induce synergistic cytotoxicity in HNSCC cells through targeting the activation and trafficking of the EGFR.

Lovastatin induces multiple stress pathways including LKB1/AMPK activation that regulate its cytotoxic effects in squamous cell carcinoma cells.

Background: Cellular stress responses trigger signaling cascades that inhibit proliferation and protein translation to help alleviate the stress or if the stress cannot be overcome induce apoptosis. In recent studies, we demonstrated the ability of lovastatin, an inhibitor of mevalonate synthesis, to induce the Integrated Stress Response as well as inhibiting epidermal growth factor receptor (EGFR) activation.

Methodology/principal Findings: In this study, we evaluated the effects of lovastatin on the activity of the LKB1/AMPK pathway that is activated upon cellular energy shortage and can interact with the above pathways.