Methods for studying stem cells: Adult stem cells for lung repair

Abstract

Recent progress in lung biology includes the description of a series of pulmonary stem and progenitor cells involved in homeostasis and regeneration of the respiratory system. Moreover, the contribution of extrapulmonary stem cells to healthy and pathological lung tissue has been observed and the developmental biology of such processes should provide important hints for understanding maintenance and repair of adult lung structure and function. Despite such remarkable advances, the phenotypic and especially the functional characterization of these stem and progenitor cells, and their derivatives, along with an understanding of the molecular cues and pathways underlying differentiation into specific respiratory lineages is still in its infancy. Accordingly, the role of endogenous and extrapulmonary stem cells in normal tissue repair and pathogenesis is still largely mysterious and added basic knowledge is required in order to explore their potential for novel regenerative therapies. This review provides an overview of the current state of the art in adult lung stem cell biology including technical aspects of isolation, characterization and differentiation, and a discussion of perspectives for future regenerative therapies.

Conditional Depletion of Airway Progenitor Cells Induces Peribronchiolar Fibrosis

“…NO 2 and ozone selectively kill ciliated cells that are regenerated by Clara cells (45,46). Acute Clara cell depletion after naphthalene treatment has a well-defined pattern of repair (1,3,6,35,(47)(48)(49)(50). Clara cells express cytochrome P450, which metabolizes naphthalene to a toxic intermediate causing cell autonomous death (49,50).…”

Identification and characterization of the human leiomyoma side population as putative tumor-initiating cells

“…A SC subpopulation, so-called side population (SP) cells, which can rapidly efflux Hoechst dye on the basis of fluorescence-activated cell-sorter analysis, has been identified in bone marrow, and its phenotype may be associated with the high-level expression of the ATP-binding cassette (ABC) transporters (21). This technique has been successfully used as a tool to identify somatic SCs (SSC) in different organs and tissues, such as bone marrow (22,23), mammary gland (24), skin (25), lung (26), dental pulp (27), endometrium (28)(29)(30), and uterine myometrium (31), as well as in tumors such as ovarian cancer (19).…”

Computational and bioengineered lungs as alternatives to whole animal, isolated organ, and cell-based lung models

“…The possibility that the lung epithelium may contain endogenous populations of progenitor cells, located in the basal layer and in the upper airways, has been suggested to be responsible for maintenance and repair of the alveolar epithelium following injury (15,45). This would support the idea that the loss or failure of these progenitor cells during senescence and disease could be accountable for the correlation between the diminution in diffusion capacity with aging and pathology (104). Three dimensional biomimetic scaffolds used in combination with lung progenitors and stem cells, specific growth factors and physical stimuli were shown to induce organotypic differentiation and lung tissue morphogenesis (115,136).…”

“…Most common lung diseases result in emphysema or fibrosis, consisting in continued pathological alteration of natural tissue morphology and leading to complete loss of lung function. Adult stem cells currently represent a potential cell source that could be used clinically for lung repair (102,104,121,137). The possibility that the lung epithelium may contain endogenous populations of progenitor cells, located in the basal layer and in the upper airways, has been suggested to be responsible for maintenance and repair of the alveolar epithelium following injury (15,45).…”