Characterization of stem cells in human airway capable of reconstituting a fully differentiated bronchial epithelium
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
The epithelia of the lung are complex structures that play an important role in normal lung physiology and are often involved in the pathophysiology of pulmonary diseases. The dynamics of cell turnover, lineage, and differentiation within these epithelia are complex and poorly understood. We have coupled the technique of retrovirus-mediated gene transfer with a xenograft model of proximal human airway to evaluate pathways of cellular proliferation and differentiation in human bronchial epithelia. Primary isolates of human bronchial epithelial cells (HBECs) were infected with mixtures of recombinant retroviruses expressing different reporter genes and seeded into denuded rat trachea, which were implanted subcutaneously into athymic mice. The HBECs were allowed to regenerate for four weeks in xenografts, which were then explanted. Clonal expansion of individual retrovirus-marked cells in the regenerated human bronchial epithelium was detected as clusters of transgene-expressing cells. Clone size varied with seeding density, resulting in the largest clones comprising 103–104 cells. A substantial number of clones showed transgene expression in basal as well as differentiated columnar cells, a finding that appeared independent of clone size. These studies demonstrate the existence of a cell type within the human bronchial epithelium that is capable of extensive self-renewal and pluripotent development. Further characterization of these potential stem cells will be important in defining pathogenesis of pulmonary diseases and in developing novel approaches to treatment such as gene therapy.
- Engelhardt, J.F., Yankaskas, J.R., Ernst, S.A., Yang, Y., Marino C.R., Boucher, R.C., Cohn, J.A., and Wilson, J.M. (1992).Nature Genet. 2:240–248. CrossRef
- Engelhardt, J.F., Zepeda, M., Cohn, J.A., Yankaskas, J.R., and Wilson, J.M. (1994).J. Clin. Invest. 93:737–749.
- Boat, T.F., Welsh, M.J., and Beaudet, A.L. (1989). InThe Metabolic Basis of Inherited Diseases, (eds.) Scriver, C.R., Beaudet, A.L., Sly, W.S., and Valle, D. (McGraw-Hill, New York), pp. 2649–2480.
- Jeffrey, P.K., and Reid, L.M. (1977). InDevelopment of the Lung, (ed.) Hodson, W.A. (Marcel Dekker, New York), pp. 87–134.
- Rennard, S.I., Beckmann, J.D. and Robbins, R.A. (1991). InThe Lung: Scientific Foundations, (eds.) Crystal, R.G., et al., (Raven Press, New York), p. 157.
- Plopper, C.G., and Hyde, D.M. (1992). InComparative Biology of the Normal Lung, (ed.) Parent, R.A. (CRC Press, Boca Raton, Florida), p. 85.
- Lane, B.P., and Gordon, R. (1974).Proc. Soc. Exp. Biol. Med. 145:1139–1144.
- Chang, L.Y., Wu, R., and Nettesheim, P. (1985).J. Cell. Sci. 74:283–301.
- Willis, R.A. (1962). InThe Borderland of Embryology and Pathology, 2nd ed., (ed.), Willis, R.A., (Butterworths, Washington), pp. 405–518.
- McDowell, E.M., Newkirk, C., and Coleman, B. (1985).Anat. Rec. 214:448–456. CrossRef
- McDowell, E.M., Ben, T., Newkirk, C., Chang, S., and De Luca, L.M. (1987).Am. J. Pathol. 129:511–522.
- Evans, M.J., Shami, S.G., Cabral-Anderson, L.J., and Dekker, N.P. (1986).Am. J. Pathol. 123:126–133.
- Snider, G.L., Lucey, E.C., Christensin, T.G., Stone, P.J., Calore, J.D., Catanese, A., and Franzblau, C. (1984).Am. Rev. Respir. Dis. 129:155–160.
- Donnelley, G.M., Haack, D.G., and Heird, C.S. (1982).Cell Tissue Kinet. 15:119–130.
- Keenan, K.P., Combs, J.W., and McDowell, E.M. (1982).Virchows Arch Cell Pathol. 41:215–229.
- Johnson, N.F., and Hubbs, A.F. (1990).Am. J. Respir. Cell. Mol. Biol. 3:579–585.
- Keenan, K.P., Wilson, T.S., and McDowell, E.M. (1983).Virchows Arch. Cell Pathol. 43:213–240.
- Engelhardt, J.F., Allen, E., and Wilson, J.M. (1991).Proc. Natl. Acad. Sci. U.S.A. 88:11192–11196.
- Ferry, N., Duplessis, O., Houssin, D., Danos, O., and Heard, J. (1991).Proc. Natl. Acad. Sci. U.S.A. 88:8377–8381.
- Schreiber, J.H., Schisa, J.A., and Wilson, J.M. (1993).Biotechniques 4 (5):818–823.
- Inayama, Y., Hook, G.E., Brody, A.R., Jetten, T.G., Mahler, J., and Nettesheim, P. (1989).Am. J. Pathol. 134:539–549.
- Goldman, M.J., Yang, Y., and Wilson, J.M. (1995).Nature Genet. 9:126–131. CrossRef
- Price, J., Turner, D., and Cepko, C. (1987).Proc. Natl. Acad. Sci. U.S.A. 84:156–160.
- Michalopoulos, G.K. (1990).FASEB J. 4:176–187.
- Sell, S. (1990).Cancer Res. 50:3811–3815.
- Jankowski, J.A., and Wright, N.A. (1992).Semin. Cell Biol. 3:445–456. CrossRef
- Potten, C.S. (1973).Cell Tissue Kinet. 7:77–88.
- Parkinson, E.K. (1992).Cell Biol. 3:435–444.
- Graham, C.J., and Pragnell, I.B. (1992).Cell Biol. 3:423–434.
- Smith, S.P., and Yee, G.C. (1992).Pharmacotherapy 12(2 Pt 2):11S-19S.
- Keller, G., and Snodgrass, R. (1990).J. Exp. Med. 171:1407–1418. CrossRef
- Potten, C.S. (1981).Int. Rev. Cytol. 69:271–318.
- Shimizu, T., Nishihara, M., Kawaguchi, S., and Sakakura, Y. (1994).Am. J. Respir. Cell Mol. Biol. 11:85–94.
- Characterization of stem cells in human airway capable of reconstituting a fully differentiated bronchial epithelium
Somatic Cell and Molecular Genetics
Volume 21, Issue 1 , pp 61-73
- Cover Date
- Print ISSN
- Online ISSN
- Kluwer Academic Publishers-Plenum Publishers
- Additional Links
- Author Affiliations
- 1. Institute for Human Gene Therapy, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
- 2. Department of Molecular and Cellular Engineering, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
- 3. The Wistar Institute, Philadelphia, Pennsylvania