Adult stem cells from bone marrow stroma differentiate into airway epithelial cells: Potential therapy for cystic fibrosis

Guoshun Wang, Bruce A. Bunnell, Richard G. Painter, Blesilda C. Quiniones, Susan Tom, Nicholas A. Lanson, Jeffrey L. Spees, Donna Bertucci, Alexandra Peister, Daniel J. Weiss, Vincent G. Valentine, Darwin J. Prockop, Jay K. Kolls

Research output: Contribution to journalArticle

238 Citations (Scopus)

Abstract

Cystic fibrosis (CF), the most prevalent, fatal genetic disorder in the Caucasian population, is caused by mutations of CF transmembrane conductance regulator (CFTR). The mutations of this chloride channel alter the transport of chloride and associated liquid and thereby impair lung defenses. Patients typically succumb to chronic bacterial infections and respiratory failure. Restoration of the abnormal CFTR function to CF airway epithelium is considered the most direct way to treat the disease. In this report, we explore the potential of adult stem cells from bone marrow, referred to as mesenchymal or marrow stromal stem cells (MSCs), to provide a therapy for CF. We found that MSCs possess the capacity of differentiating into airway epithelia. MSCs from CF patients are amenable to CFTR gene correction, and expression of CFTR does not influence the pluripotency of MSCs. Moreover, the CFTR-corrected MSCs from CF patients are able to contribute to apical Cl- secretion in response to cAMP agonist stimulation, suggesting the possibility of developing cell-based therapy for CF. The ex vivo coculture system established in this report offers an invaluable approach for selection of stem-cell populations that may have greater potency in lung differentiation.

Original languageEnglish (US)
Pages (from-to)186-191
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number1
DOIs
StatePublished - Jan 4 2005
Externally publishedYes

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Adult Stem Cells
Cell- and Tissue-Based Therapy
Cystic Fibrosis
Stromal Cells
Stem Cells
Bone Marrow
Epithelial Cells
Epithelium
Cystic Fibrosis Transmembrane Conductance Regulator
Lung
Mutation
Inborn Genetic Diseases
Chloride Channels
Regulator Genes
Coculture Techniques
Bacterial Infections
Respiratory Insufficiency
Population
Chlorides
Gene Expression

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Adult stem cells from bone marrow stroma differentiate into airway epithelial cells : Potential therapy for cystic fibrosis. / Wang, Guoshun; Bunnell, Bruce A.; Painter, Richard G.; Quiniones, Blesilda C.; Tom, Susan; Lanson, Nicholas A.; Spees, Jeffrey L.; Bertucci, Donna; Peister, Alexandra; Weiss, Daniel J.; Valentine, Vincent G.; Prockop, Darwin J.; Kolls, Jay K.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 1, 04.01.2005, p. 186-191.

Research output: Contribution to journalArticle

Wang, G, Bunnell, BA, Painter, RG, Quiniones, BC, Tom, S, Lanson, NA, Spees, JL, Bertucci, D, Peister, A, Weiss, DJ, Valentine, VG, Prockop, DJ & Kolls, JK 2005, 'Adult stem cells from bone marrow stroma differentiate into airway epithelial cells: Potential therapy for cystic fibrosis', Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 1, pp. 186-191. https://doi.org/10.1073/pnas.0406266102
Wang, Guoshun ; Bunnell, Bruce A. ; Painter, Richard G. ; Quiniones, Blesilda C. ; Tom, Susan ; Lanson, Nicholas A. ; Spees, Jeffrey L. ; Bertucci, Donna ; Peister, Alexandra ; Weiss, Daniel J. ; Valentine, Vincent G. ; Prockop, Darwin J. ; Kolls, Jay K. / Adult stem cells from bone marrow stroma differentiate into airway epithelial cells : Potential therapy for cystic fibrosis. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 1. pp. 186-191.
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