The Tissue Core provides expertise, guidance, and standardized methodology for performing lung structural analysis including inflation, fixation, immunohistochemistry, laser capture micro dissection, fluorescence in situ hybridization (FISH), and morphometric analysis. The Core assists with precise site-specific isolation of vascular tissue including micro-dissection techniques and comparison of phenotypic differences between proximal and distal cells. The Core efficiently provides a wide variety of freshly dispersed and cultured resident vascular cells isolated, grown, and, characterized in a standardized way. Available cells include vascular smooth muscle cells, endothelial cells, and adventitial fibroblasts harvested from rodent, bovine and human tissue. The Core uses immunofluorescent staining with cell-type-specific antibody probes to document identity, extent of homogeneity or heterogeneity, and cell-culture-induced changes in differentiation. Cell sorting capability is available to improve purity and yield of harvested microvascular cell populations. The Core routinely performs in vitro cell proliferation, toxicity, apoptosis, and migration assays. Digital imaging is used to catalogue the morphological appearance of cell populations after initial isolation. The Core assists with application of short and long-term hypoxic and mechanical stress stimulation to freshly dispersed and cultured cells and the use of co-culture techniques to assess the potential modulatory role of neighboring vascular cells. The Core achieves economies of scale through centralized processing of vascular cells and bulk ordering of supplies. Additional responsibilities of the Core include: coordinated maintenance and upgrading of tissue-culture equipment;short-term radioactive waste management; restocking and maintenance of radioisotope work area;and ongoing training of fellows, research staff and student workers in staining, imaging and cell culture techniques. The Core facilitates assess to human lung tissue through the Lung Tissue Research Consortium.

Public Health Relevance

The Tissue Core encourages a consistent approach to the measurement of structural changes and gene expression in lung and heart in response to various forms of stress. The Core facilitates the isolation of precisely characterized vascular cell populations for mechanistic studies. The results provide important information about how pulmonary hypertension occurs and may be treated more effectively in the future.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL014985-40
Application #
8502293
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
40
Fiscal Year
2013
Total Cost
$251,238
Indirect Cost
$86,504
Name
University of Colorado Denver
Department
Type
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Ding, Yonghui; Xu, Xin; Sharma, Sadhana et al. (2018) Biomimetic soft fibrous hydrogels for contractile and pharmacologically responsive smooth muscle. Acta Biomater 74:121-130
Kumar, Rahul; Graham, Brian (2018) How does inflammation contribute to pulmonary hypertension? Eur Respir J 51:
Jiang, Xinguo; Nicolls, Mark R; Tian, Wen et al. (2018) Lymphatic Dysfunction, Leukotrienes, and Lymphedema. Annu Rev Physiol 80:49-70
Schäfer, Michal; Humphries, Stephen; Stenmark, Kurt R et al. (2018) 4D-flow cardiac magnetic resonance-derived vorticity is sensitive marker of left ventricular diastolic dysfunction in patients with mild-to-moderate chronic obstructive pulmonary disease. Eur Heart J Cardiovasc Imaging 19:415-424
D'Alessandro, Angelo; El Kasmi, Karim C; Plecitá-Hlavatá, Lydie et al. (2018) Hallmarks of Pulmonary Hypertension: Mesenchymal and Inflammatory Cell Metabolic Reprogramming. Antioxid Redox Signal 28:230-250
Karoor, Vijaya; Fini, Mehdi A; Loomis, Zoe et al. (2018) Sustained Activation of Rho GTPases Promotes a Synthetic Pulmonary Artery Smooth Muscle Cell Phenotype in Neprilysin Null Mice. Arterioscler Thromb Vasc Biol 38:154-163
Stenmark, Kurt R; Graham, Brian B (2018) Urocortin 2: will a drug targeting both the vasculature and the right ventricle be the future of pulmonary hypertension therapy? Cardiovasc Res 114:1057-1059
Madhavan, Krishna; Frid, Maria G; Hunter, Kendall et al. (2018) Development of an electrospun biomimetic polyurea scaffold suitable for vascular grafting. J Biomed Mater Res B Appl Biomater 106:278-290
Stenmark, Kurt R; Frid, Maria G; Graham, Brian B et al. (2018) Dynamic and diverse changes in the functional properties of vascular smooth muscle cells in pulmonary hypertension. Cardiovasc Res 114:551-564
Schäfer, Michal; Kheyfets, Vitaly O; Barker, Alex J et al. (2018) Reduced shear stress and associated aortic deformation in the thoracic aorta of patients with chronic obstructive pulmonary disease. J Vasc Surg 68:246-253

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