Rare Daily Staff

Researchers at the University of Adelaide showed that cells causing the rare genetic disorder cystic fibrosis could be successfully replaced with healthy ones in mouse models of the disease using an innovative transplantation method.

Cystic fibrosis is a rare, life-shortening genetic disease. It is caused by a defective or missing cystic fibrosis transmembrane conductance regulator, or CFTR protein. There are approximately 2,000 known mutations in the CFTR gene. Some of these mutations, which can be determined by a genetic test or genotyping test, lead to CF by creating non-working or too few CFTR proteins at the cell surface.

The defective function or absence of CFTR protein results in poor flow of salt and water into and out of the cell in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage in many patients that eventually leads to death.

The researchers were working with stem cell transplantation of adult stem cells harvested from the lungs of CF patients that have been corrected using gene therapy, and then would be reintroduced back into those patients. The idea behind such an approach is that the new transplanted adult stem cells pass on their healthy genes to their daughter cells providing a constant means to replenish the airways with healthy cells and combat the onset of cystic fibrosis.

The problem, as shown in mice, is that delivering the cells into unconditioned mouse airways led to inefficient engraftment. The researchers speculated that if they could disrupt the epithelial cell layer using the sclerosing agent polidocanol that essentially knocks out the top layer of cells, it might facilitate effective transplantation of cultured stem cells in mouse nasal airways.

The research, published in the journal Stem Cell Research and Therapy, applies cell transplantation therapy, used in bone marrow transplants to treat immunodeficiency disorders. It showed that the method they developed extended the presence of functioning cells in the mouse airways and could provide a feasible means of development of a way to deliver such therapies in humans.

“The key to these successful transplantations was our innovative method. We first eliminated the existing surface cells, which then created the space required to introduce the new cells,” said Nigel Farrow, a post-doctoral research fellow from the University of Adelaide’s Robinson Research Institute and lead author of the study. “If we can perfect this technique, it will accelerate this exciting research which could significantly improve the lives of those living with cystic fibrosis and potentially combat this chronic life-limiting illness.”

August 21, 2018
Photo: Nigel Farrow, a post-doctoral research fellow from the University of Adelaide’s Robinson Research Institute

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