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063 Reagents for Studying Human Lung Cell Biology and Cellular Function

NHLBI SBIR/STTR Contract Topic

(Fast-Track proposals will be accepted.) Number of anticipated awards: 4-6

Approximately half of the 44 cells that comprise the human respiratory tract still remain partially identified and their function(s) is incompletely understood (Franks et. al. Proc Am Thorac Soc 2008; 5: 763-6)). Suitable technologies are available to identify, sort, purify, culture, and determine cell surface markers or other unique identifying features that permit individual characterization of cell types. It seems feasible to unravel the origins and functional capabilities of lung cells involved in developmental stages of lung growth and in disease. But it will be necessary to generate new reagents that will identify these still incompletely characterized cells in the human lung, permit establishment of cell lines, and facilitate ready isolation from lung tissue.

Much is known already about many important cells in the human respiratory tract, but little is known about the supportive function of structural cells, the para-endocrine effect(s) of lung cells, and the location and functions of stem and progenitor cells that remain quiescent until stimulated to help repair tissue after injury or disease. Cellular functions that suppress or create apoptosis to reestablish normalcy need insight. Several examples are offered representing the three main compartments of the lung:

  1. Among airway cells comprising the large and small airways of the human bronchial tree, the ciliated, columnar, secretory, and basal cells have been well studied, but more knowledge about epithelial stem and progenitor cells along the airways, mucus and ciliated cell interactions, functions of brush cells, and the stimuli from neuro-endocrine cells to affect integrity of the epithelium, all are needed.
  2. In the alveolus, information is considerable about Type I cells, the multiple tasks of Type II cells, and surfactant production and properties, but Type II cell stimulated epithelial to mesenchymal transition is evolving but is not understood as a process leading to lung fibrosis, and the activity of interstitially located fibroblasts to secrete extracellular matrix needs more scrutiny.
  3. The vascular bed of the pulmonary circulation needs study of the endothelial cells populating different locations and the capillary network, and interactions of endothelium with smooth muscle cells and with adventitial fibroblasts need examination.

Thus, special reagents are needed for studying lung cell biology and cells involved in organ development, growth, and disease. Examples of needed reagents include:

  1. Antibodies that will recognize specific cell types and permit separation and recovery of cells from micro- dissected lung tissue.
  2. Reagents to identify proteomic products produced by cells.
  3. Antibodies that recognize cell surface markers that can help identify and track different cell lineages present in airway and alveolar structures.
  4. Specific antibodies to recognize cell surface markers that help to separate out individual cell types from among heterogeneous lung tissue cells.
  5. Reagents that track cellular changes in differentiation as development occurs, track cells that enter latency, and detect signals of re-stimulation or redeployment for repair tasks.
  6. Reagents that characterize and identify “stem” and progenitor lung cells.

Phase I proposals should focus on development of reagents that identify unique cell surface markers or other special structures that would permit extraction of cells, considered to be incompletely characterized or identified, from human lung tissue biopsy specimens, or other lung bio-specimens such as transbronchial biopsy and bronchoalveolar lavage. This should lead to cell separation and establishment of in vitro cell cultures.

Phase II proposals should focus on scale up production of unique reagents for cell separation that can be placed in a repository for use by other investigators by application to investigate lung disease, and to study cell proteomics and other functions.

For more information, contact OTAC.

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Last Updated December 2011

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