An induced pluripotent stem cell (iPS)-based approach for the repopulation and phenotypic correction of cystic fibrosis airway epithelium

LOI, ROBERTO

2011-01-01

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Abstract

Background. In cystic fibrosis, the repopulation of diseased airway epithelium with cells expressing functional CFTR represents an option that may be available in the future to reduce morbidity and mortality of this disease. The recently developed induced pluripotent stem cells (iPS) allowed the generation of patient-specific stem cells that may be useful for cell therapy approaches. For instance, in cystic fibrosis, diseased lung epithelium could potentially be replaced by functional epithelial cells derived from iPS. iPS could be generated from the patient’s somatic cells, and the gene defect could be corrected in vitro. Then, iPS could be induced to differentiate in vitro into airway epithelial cells and these cells could be infused to the same patient, thus avoiding immune rejection, to repopulate the diseased airway epithelium with normal cells. This is a very ambitious goal, and many issues need to be solved before this approach becomes applicable to human treatment in the future. The induction of differentiation of iPS into bronchial epithelial cells still represents a difficult task, since our knowledge of the mechanisms that guide this differentiation process are still limited. Recent studies suggest that iPS cells derived from airway epithelial cells may possess a stronger differentiation potential towards airway epithelial lineages than iPS cells derived from other cell types. Objectives. Therefore we proposed to derive iPS cells from airway epithelial cells, either normal or from patients affected by cystic fibrosis Project status. Within the first year of the project we induced the reprogramming of human airway epithelial cells, normal and CF, that should determine the development of iPS cells. We are now at the end of the first year of the project and we are involved in the analysis of the cell cultures for the presence of iPS colonies, that will be isolated and characterized. During the second year we will induce the differentiation of iPS cells into airway epithelial cells. Spin-off for research & clinical purposes. This study should clarify whether iPS cells derived form airway epithelial cells have a higher differentiation potential towards lung epithelium. This knowledge is relevant for a potential future application of iPS cells in the repopulation of CF lung epithelium with functional cells.