This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 2008-0018OCv1 40/6/717    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Dannhoffer, L. Articles by Chinet, T. Search for Related Content PubMed PubMed Citation Articles by Dannhoffer, L. Articles by Chinet, T.

Functional Properties of Mixed Cystic Fibrosis and Normal Bronchial Epithelial Cell Cultures

¹ Université de Versailles Saint Quentin en Yvelines, UPRES EA 220, Laboratoire de Biologie et Pharmacologie des Epithéliums Respiratoires, UFR Paris Ile de France Ouest, Boulogne, France; and ² Assistance Publique - Hôpitaux de Paris, Hôpital Ambroise Paré, Service d'Anatomie Pathologique, Boulogne, France

Correspondence and requests for reprints should be addressed to Thierry Chinet, M.D., Service de Pneumologie, Hôpital Ambroise Paré, 9, avenue Charles de Gaulle, 92104 Boulogne-Billancourt cedex, France. E-mail: thierry.chinet{at}apr.aphp.fr

Cystic fibrosis (CF) airway epithelia exhibit altered Cl^– and Na⁺ transport properties and increased IL-8 secretion. In the present study, we examined whether a small proportion of cells with a normal phenotype could normalize the ion transport and IL-8 secretion properties of a CF airway epithelial cell layer. We obtained three types of primary cultures of human bronchial epithelial cells: one composed of 100% non-CF cells, one of 100% CF cells, and one of 10% non-CF and 90% CF cells ("cocultures"). Measurement of the bioelectric properties in Ussing chambers revealed that the cocultures displayed Cl^– and Na⁺ transports similar to those observed in the 100% non-CF cultures and significantly different from CF cultures. IL-8 concentration in the coculture supernatant was not different from non-CF cultures, but was significantly lower than in CF cultures. This study provides evidence that 10% bronchial epithelial cells expressing a normal phenotype are sufficient to functionally correct a primary culture of CF bronchial epithelial cells in vitro. We postulate that 10% cells with a non-CF phenotype can be used as a goal for the design of gene therapy and cell therapy trials for CF lung disease.

Key Words: gene therapy • cell therapy • ion transport • genetic diseases • bronchial diseases

CLINICAL RELEVANCE Mixed cultures containing 90% cystic fibrosis (CF) and 10% non-CF human bronchial epithelial cells display normal ion transport properties and IL-8 secretion. This result can be used as a goal for the design of gene therapy and cell therapy trials for CF lung disease.