[Show abstract][Hide abstract] 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.
Proceedings of the National Academy of Sciences 02/2005; 102(1):186-91. DOI:10.1073/pnas.0406266102 · 9.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The transcriptional profile of Pseudomonas aeruginosa after interactions with primary normal human airway epithelial cells was determined using Affymetrix GeneChip technology.
Gene expression profiles indicated that various genes involved in phosphate acquisition and iron scavenging were differentially
Infection and Immunity 10/2004; 72(9):5433-8. DOI:10.1128/IAI.72.9.5433-5438.2004 · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Molecular Therapy (2004) 9, S195–S195; doi: 10.1016/j.ymthe.2004.06.455
514. Potential of Bone Marrow Mesenchymal Stem Cells for Cystic Fibrosis Therapy
Guoshun Wang1,*, Bruce A. Bunnell2,*, Richard G. Painter1, Susan Tom2, Nicholas A. Lanson1, Jeffery L. Spees2, Donna Bertucci1, Daniel J. Weiss3, Vincent G. Valentine4, Darwin J. Prockop2 and Jay K. Kolls11Center for Gene Therapy, Departments of Medicine and Genetics, Louisiana State University Health Sciences Center, New Orleans, LA2Center for Gene Therapy, Departments of Medicine and Pharmocology, Tulane University Health Sciences Center, New Orleans, LA3Pulmonary and Critical Care Section, Department of Medicine, Vermont Lung Center, University of Vermont School of Medicine, Burlington, VT4Lung Transplantation Program, Ochsner Clinic Foundation, New Orleans, LA5Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA*Drs. GW and BAB contribute equally