Building a better model

A good percentage of ISSCR 2014 was dedicated to the development of model systems that better reflected human pathophysiology. As California Institute for Regenerative Medicine Senior Scientific Advisor Alan Trounson indicated, rodent models have not served the scientific community particularly well as they often don’t represent the heterogeneity of human disease. Furthermore, he challenged, gene knockout models have limited utility because they don’t really model diseases that involve more than one gene, which given the complexity of cellular signalling systems, for example, tends to be most conditions.

Several presentations and posters therefore focused on the application of stem cell technologies to construct more accurate models of human disease using human cells, both diseased and healthy, and within a more tissue- or organ-like context.

Researchers at the BC Cancer Agency and STEMCELL Technologies, for example, described their efforts to construct an in-vitro model of the human airway by growing human bronchial epithelial cells in PneumaCult medium. This allows the cells to function at the air-liquid interface and thus mimic in vivo airway functions to understand, for example, viral infection, drug transport and bronchial disease.

Leiden University’s Christine Mummery, meanwhile, talked about the challenges of studying cardiac ion channels not only in mouse models, which offer a very different physiology from humans, but even between cultures of diseased and control human cardiomyocytes. Mummery’s approach was to develop isogenic pairs of cell lines, correcting the mutation within a patient sample to use as a control for the original patient sample. Drugs can then be tested on these pairs to determine with certainty that the results are due to the mutation and not background genetic anomalies between cell lines.

Other such efforts will be described in “Modestly modeled” in the July issue of DDNews and in a special feature on disease modeling in the November issue.