Assessing Human Airway Epithelial Progenitor Cells for Cystic Fibrosis Cell Therapy.

Assessing Human Airway Epithelial Progenitor Cells for Cystic Fibrosis Cell Therapy. Am J Respir Cell Mol Biol. 2020 May 21;: Authors: Lee RE, Miller SM, Mascenik TM, Lewis CA, Dang H, Boggs ZH, Tarran R, Randell SH Abstract Cystic fibrosis (CF) is caused by loss-of-function mutations in the CF transmembrane regulator (CFTR) gene. Pharmacologic therapies directed at CFTR have been developed but are not effective for mutations that result in little or no mRNA or protein expression. Cell therapy is a potential mutation-agnostic approach to treatment. One strategy is to harvest human bronchial epithelial cells (HBECs) for gene addition or genetic correction, followed by expansion and engraftment. This approach will require cells to grow extensively while retaining their ability to reconstitute CFTR activity. We hypothesized that conditionally reprogrammed cell (CRC) technology, namely growth in the presence of irradiated feeder cells and a Rho kinase inhibitor, would enable expansion while maintaining cell capacity to express functional CFTR. Our goal was to compare expression of the basal cell marker NGFR and 3D bronchosphere colony forming efficiency (CFE) in early and later passage HBECs grown using non-proprietary bronchial epithelial growth medium or the CRC method. Cell number and CFTR activity were determined in a competitive repopulation assay employing chimeric air-liquid interface (ALI) cultures. HBECs expanded using the CRC m...
Source: American Journal of Respiratory Cell and Molecular Biology - Category: Molecular Biology Authors: Tags: Am J Respir Cell Mol Biol Source Type: research