Metabolic Enzymes in Sarcomagenesis: Progress Toward Biology and Therapy.

Cellular metabolism reprogramming is an emerging hallmark of cancer, which provides tumor cells with not only necessary energy but also crucial materials to support growth. Exploiting the unique features of cancer metabolism is promising in cancer therapies. The growing interest in this field has led to numerous inhibitors being developed against key molecules in metabolic pathways, though most of them are still in preclinical development.

Treatment with a Small Molecule Mutant IDH1 Inhibitor Suppresses Tumorigenic Activity and Decreases Production of the Oncometabolite 2-Hydroxyglutarate in Human Chondrosarcoma Cells.

Chondrosarcomas are malignant bone tumors that produce cartilaginous matrix. Mutations in isocitrate dehydrogenase enzymes (IDH1/2) were recently described in several cancers including chondrosarcomas. The IDH1 inhibitor AGI-5198 abrogates the ability of mutant IDH1 to produce the oncometabolite D-2 hydroxyglutarate (D-2HG) in gliomas.

Epigenetic regulation of embryonic stem cell marker miR302C in human chondrosarcoma as determinant of antiproliferative activity of proline-rich polypeptide 1.

Metastatic chondrosarcoma of mesenchymal origin is the second most common bone malignancy and does not respond either to chemotherapy or radiation; therefore, the search for new therapies is relevant and urgent. We described recently that tumor growth inhibiting cytostatic proline-rich polypeptide 1, (PRP-1) significantly upregulated tumor suppressor miRNAs, downregulated onco-miRNAs in human chondrosarcoma JJ012 cell line, compared to chondrocytes culture. In this study we hypothesized the existence and regulation of a functional marker in cancer stem cells, correlated to peptides antiproliferative activity.

Micropatterning cells on permeable membrane filters.

Epithelium is abundantly present in the human body as it lines most major organs. Therefore, ensuring the proper function of epithelium is pivotal for successfully engineering whole organ replacements. An important characteristic of mature epithelium is apical-basal polarization which can be obtained using the air-liquid interface (ALI) culture system.

Challenges and opportunities for tissue-engineering polarized epithelium.

The epithelium is one of the most important tissue types in the body and the specific organization of the epithelial cells in these tissues is important for achieving appropriate function. Since many tissues contain an epithelial component, engineering functional epithelium and understanding the factors that control epithelial maturation and organization are important for generating whole artificial organ replacements. Furthermore, disruption of the cellular organization leads to tissue malfunction and disease; therefore, engineered epithelium could provide a valuable in vitro model to study disease phenotypes.

Tools for micropatterning epithelial cells into microcolonies on transwell filter substrates.

Despite the importance of epithelial tissue in most major organs there have been limited attempts to tissue engineer artificial epithelium. A key feature of mature epithelium is the presence of an apical-basal polarization, which develops over 7-20 days in culture. Currently, the most widely used 2D system to generate polarized epithelium in vitro involves the filter insert culture system, however this system is expensive, laborious and requires large numbers of cells per sample.

Proteomics identifies multipotent and low oncogenic risk stem cells of the spleen.

The adult spleen harbors a population of naturally occurring multipotent stem cells of non-lymphoid lineage (CD45-). In animal models, these splenic stem cells can directly or indirectly contribute to regeneration of bone, inner ear, cranial nerves, islets, hearts and salivary glands. Here we characterize the CD45- stem cell proteome to determine its potential broader multipotency versus its protection from malignant transformation.

Engineering functional islets from cultured cells.

Objective: Although pancreatic islet transplantation can now be performed minimally invasively in patients with type 1 diabetes, the availability of functional islet donors remains the chief obstacle to widespread clinical application. Tissue engineering islet cells in vitro that function when implanted in vivo provides a solution to this problem.

Research Design And Methods: Rat pancreatic islets were enzymatically dissociated into a single-cell suspension and seeded onto a polyglycolic acid (PGA) scaffold.

Bioengineered three-layered robust and elastic artery using hemodynamically-equivalent pulsatile bioreactor.

Background: There is an essential demand for tissue engineered autologous small-diameter vascular graft, which can function in arterial high pressure and flow circulation. We investigated the potential to engineer a three-layered robust and elastic artery using a novel hemodynamically-equivalent pulsatile bioreactor.

Methods And Results: Endothelial cells (ECs), smooth muscle cells (SMCs), and fibroblasts were harvested from bovine aorta.

Tissue engineered cartilage "bioshell" protective layer for subcutaneous implants.

Objective: One current technique to reconstruct an ear for microtia involves the use of a high density polyethylene auricular implant; however, the implant can extrude if not covered in a temporoparietal fascia flap. Theoretically, an autologous tissue engineered cartilage "bioshell" protective coating around a permanent biocompatible implant might reduce potential extrusion to avoid the flap requirement. We hypothesized that if subjected to intentional exposure, a bioshell coating over an implant would provide enhanced wound healing.