New Frontiers in Cystic Fibrosis Therapy: The Case of Stem Cells

Cystic fibrosis (CF) is an autosomal recessive inherited disorder that affects ~80,000 individuals worldwide. Mutations in the CF transmembrane conductance regulator gene (CFTR) cause dysfunction of the CFTR protein, a cAMP- and PKA-activated chloride channel. Decades of research and development have made great progress in molecular understanding and clinical care of this disease, which has dramatically extended the patient median life expectancy to over 40 years. However, this devastating disease remains incurable, with lung pathology the most common cause of morbidity and mortality. Stem cells maintain the capacity of self-renewal and induced differentiation, thus holding promise for CF therapy. While early studies generated the excitement of lung engraftment and regeneration by different origins of stem cells, several encountered obstacles impede viable development of this strategy into a feasible therapy. This review article will provide an update of the research and discuss the major challenges facing the field. Moreover, new emerging technologies, such as CRISPR/Cas9 genomic editing, make possible the precise correction of the CFTR defect in situ. Potential impacts of these advancements on future prospects of CF stem cell therapy will be highlighted.