Journal Club

Journal Club

Stay in the Loop on Stem Cell research technology and Cystic fibrosis.

Targeted Correction and Restored Function of the CFTR Gene in Cystic Fibrosis Induced Pluripotent Stem Cells. Crane et al., Stem Cell Reports (August 2015)


Moderator: Oluwaseun (Sean) Ojo

Category: Scientific article/RSF interest

In this article, Crane et al., show the potential for using stem cell cells in lung diseases such as cystic fibrosis.  Specifically, they utilized a range of novel techniques including reprogramming and homology-directed repair (HDR) to edit the CFTR locus and correct inherited genetic mutations linked to cystic fibrosis. Briefly, the authors generated induced pluripotent stem cells (iPSCs) cells from compound heterozygous (ΔF508/ ΔI507) cystic fibrosis primary fibroblasts by reprogramming these cells using viral vectors that encoded reprogramming transcription factors OCT4, SOX2, KLF4, C-MYC, and NANOG. Using the zinc-finger nuclease mediated HDR; the CFTR gene was corrected in cystic fibrosis iPSCs. The authors further showed that the correction restored, 1) protein expression of mature CFTR glycoprotein,  2) CFTR chloride channel activity (via Ussing chamber assay) and 3) CFTR chloride channel function to cAMP-sensitive CFTR anion transport (iodide efflux analysis)  in IPSCs derived lung epithelial cells.

This work on CFTR mutation and cystic fibrosis and others on alpha 1-antitrypsin deficiency and emphysema clearly demonstrate the importance of de novo engineered iPSC derived lung cells in correcting and treating pulmonary diseases. Additionally, they pinpoint the importance of stem cell biology and highlight the future and hope of stem cell research to potentially accelerate development of new treatments for several diseases.

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