University of Glasgow researchers have used what is described as the first bioengineered bone marrow model for cancer research to test a cutting-edge immunotherapy, with sobering results. The team placed leukaemic haematopoietic stem cells into synthetic peptide hydrogels engineered to mimic the bone marrow niche, then challenged them with a combined CRISPR and CAR T-cell therapy directed at acute myeloid leukaemia, described in the study as the most common leukaemia in adults.
The comparison with conventional methods was revealing. Standard testing, in which cells are grown on the flat plastic of a Petri dish, overestimated the therapy's effectiveness and failed to detect its harmful effects on healthy cells. The bioengineered marrow caught both problems, suggesting that three-dimensional tissue mimics can expose weaknesses in candidate treatments long before they reach patients, and could reduce reliance on animal testing in the drug development pipeline.
The study, from Glasgow's School of Molecular Biosciences with research fellow Dr Hannah Donnelly among the lead authors, is published in Biomaterials. The researchers stress the work is early-stage, with benefits expected to emerge over the next decade, but argue the approach could make drug development more accurate and humane. The research was funded by the Biotechnology and Biological Sciences Research Council and the Engineering and Physical Sciences Research Council.