Evidence for Human Lung Stem Cells

Abstract

BACKGROUND Although progenitor cells have been described in distinct anatomical regions of the lung, description of resident stem cells has remained elusive. METHODS Surgical lung-tissue specimens were studied in situ to identify and characterize human lung stem cells. We defined their phenotype and functional properties in vitro and in vivo. RESULTS Human lungs contain undifferentiated human lung stem cells nested in niches in the distal airways. These cells are self-renewing, clonogenic, and multipotent in vitro. After injection into damaged mouse lung in vivo, human lung stem cells form human bronchioles, alveoli, and pulmonary vessels integrated structurally and functionally with the damaged organ. The formation of a chimeric lung was confirmed by detection of human transcripts for epithelial and vascular genes. In addition, the self-renewal and long-term proliferation of human lung stem cells was shown in serial-transplantation assays. CONCLUSIONS Human lungs contain identifiable stem cells. In animal models, these cells participate in tissue homeostasis and regeneration. They have the undemonstrated potential to promote tissue restoration in patients with lung disease. (Funded by the National Institutes of Health.)

Comparative study of immune regulatory properties of stem cells derived from different tissues

“…CSCs and LSCs (three samples each) were obtained from enzymatic dissociation of myocardial and lung tissues, respectively, and cultured as adherent cells as previously described [50,53].…”

“…All experiments were performed between passages 2 and 6. Full characterization of CSCs and LSCs has been already described by our group elsewhere [50,53].…”

“…Each SC type was characterized in terms of phenotype and differentiation potential [22,44,50,53,54] following International Society for Cellular Therapy (ISCT)-minimal criteria [55].…”

“…To test this hypothesis, we studied (1) BM-MSCs [25]; (2) olfactory ectomesenchymal SCs (OEMSCs), which are distributed in the olfactory lamina propria and induce neurogenesis, and restore the hippocampal neuronal network [44][45][46]; (3) non-MSC leptomeningeal SCs (LeSCs), described by us first in rats as nestin-positive cells capable of differentiating into neuronal, astrocyte, and oligodendrocyte precursors [47,48] and, more recently, in mice and humans (personal observation); and (4) human c-Kitpositive SCs isolated from the amniotic fluid (AFSCs) [49], from the adult heart (cardiac SCs: CSCs) [50][51][52]; and adult lung SCs (LSCs) [53]. AFSCs are multipotent, nonteratogenic cells with characteristics intermediate between embryonic and adult SCs [49].…”

“…AFSCs are multipotent, nonteratogenic cells with characteristics intermediate between embryonic and adult SCs [49]. CSCs are multipotent cells capable of differentiating into cardiomyocytes and coronary vessels [50][51][52], while LSCs form lung structures of both endodermal and mesodermal origin [53]. The standardized approach previously introduced to characterize MSCs [25] was applied to all SCs to define their immunological profile.…”