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Surgical management of long segment tracheal disease is limited by a paucity of donor tissue and poor performance of synthetic materials. A potential solution is the development of a tissue-engineered tracheal graft (TETG) which promises an autologous airway conduit with growth capacity.We created a TETG by vacuum seeding bone marrow-derived mononuclear cells (BM-MNCs) on a polymeric nanofiber scaffold. First, we evaluated the role of scaffold porosity on cell seeding efficiency in vitro. We then determined the effect of cell seeding on graft performance in vivo using an ovine model.Seeding efficiency of normal porosity (NP) grafts was significantly increased when compared to high porosity (HP) grafts (NP: 360.3 ± 69.19 × 10(3) cells/mm(2); HP: 133.7 ± 22.73 × 10(3) cells/mm(2); p0.004). Lambs received unseeded (n=2) or seeded (n=3) NP scaffolds as tracheal interposition grafts for 6 weeks. Three animals were terminated early owing to respiratory complications (n=2 unseeded, n=1 seeded). Seeded TETG explants demonstrated wound healing, epithelial migration, and delayed stenosis when compared to their unseeded counterparts.Vacuum seeding BM-MNCs on nanofiber scaffolds for immediate implantation as tracheal interposition grafts is a viable approach to generate TETGs, but further preclinical research is warranted before advocating this technology for clinical application.

Patients who undergo implantation of a tissue-engineered vascular graft (TEVG) for congenital cardiac anomalies are monitored with echocardiography, followed by magnetic resonance imaging or angiography when indicated. While these methods provide data regarding the lumen, minimal information regarding neotissue formation is obtained. Intravascular ultrasound (IVUS) has previously been used in a variety of conditions to evaluate the vessel wall. The purpose of this study was to evaluate the utility of IVUS for evaluation of TEVGs in our ovine model. Eight sheep underwent implantation of TEVGs either unseeded or seeded with bone marrow-derived mononuclear cells. Angiography, IVUS, and histology were directly compared. Endothelium, tunica media, and graft were identifiable on IVUS and histology at multiple time points. There was strong agreement between IVUS and angiography for evaluation of luminal diameter. IVUS offers a valuable tool to evaluate the changes within TEVGs, and clinical translation of this application is warranted.

Breast cancer is the second most common type of cancer among women with an expected ∼192,000 newly diagnosed cases in the United States this year alone. Early detection methods are becoming increasingly important for guiding treatment options and decisions. Currently, standard molecular diagnostic tests of breast cancer characterize patient cases by estrogen receptor (ER), progesterone receptor (PR) and Her2neu status. The recently discovered biomolecule, microRNA (miRNA), is being assessed as a novel diagnostic tool; however, since miRNA is a regulatory molecule it is likely that expression is cell-type and location specific, thus studies that don't specifically study malignant and normal cells may mask miRNA patterns within tissue. The goal of our study was to evaluate miRNA expression within sub-regions of formalin-fixed paraffin-embedded breast cancer tissue. Utilizing a combination of laser-based and manual microdissection techniques, we evaluated the expression of several breast cancer associated miRNA via TaqMan chemistry. We dissected selected areas of tumor and normal cells, as well as a grid-like pattern over entire tissue sections to separately evaluate each histopathological region. The data suggest there is heterogeneity of miRNA expression within the tumor and the surrounding normal tissue. In order study this phenomenon in more detail, we are now adapting a new two-dimensional amplification (2D-PCR) device to measure miRNA levels across tissue specimens with fine resolution. This approach to examining miRNA profiles in tissue sections may lead to novel findings with diagnostic or prognostic implications for breast cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2999.