National Heart, Lung, and Blood Institute perspective: lung progenitor and stem cells--gaps in knowledge and future opportunities

Abstract

Because the lung stem cell field is so new, there remain many unanswered questions that are being addressed regarding the identification, location, and role of exogenous and endogenous stem and progenitor cell populations in growth, regeneration, and repair of the lung. Advancing lung stem cell biology will require multidisciplinary teams and a long term effort to unravel the biologic processes of stem cells in the lung. While no clinical research in lung stem cell therapies are currently funded by NHLBI, the knowledge gained by understanding the basic biology of the lung stem cell populations will be needed to translate to diagnostic and therapeutic strategies in the future.

Figure 1

Number of National Heart, Lung, and Blood Institute-supported grants in lung stem/progenitor cell biology (2001-2008). New refers to new applications (type 1 or 2) to the NIH. Abbreviation: DLD, Division of Lung Diseases.

Figure 2

Illustration of putative stem cell niches in the adult mouse lung. Epithelia of the adult mouse lung can be divided into four major, biologically distinct trophic units (trachea, bronchi, bronchioles, and alveoli), each of which encompasses unique types of airway epithelial cells (epithelia relevant to each unit are shown inside circles). Five potential stem cell niches for these various trophic units are shown on the right, with locations of candidate stem cells marked by arrowheads (cells are in red). Stem cells and niches include the following: 1, an unknown cell type in the SMG ducts of the proximal trachea; 2, basal cells in the intercartilaginous zones of the lower trachea and bronchi (these structures may also be associated with innervated NEBs; 3, variant Clara cells associated with NEBs in bronchioles; 4, Clara cell associated with BADJ; and 5, alveolar type II cells of the alveoli. Abbreviations: BADJ, bronchiolar alveolar duct junctions; Clara^v, variant Clara cells; NEB, neuroendocrine body; SMG, submucosal gland. (From Liu X, Engelhardt JF. The glandular stem/progenitor cell niche in airway development and repair. Proc Am Thorac Soc 2008;5:682-688.)