Researchers at the University of Glasgow have created the first bioengineered human bone marrow model, marking a significant step forward in cancer research and reducing reliance on animal testing.
The study, published in Biomaterials, demonstrates how the model can be used to assess emerging therapies for acute myeloid leukaemia (AML), the most common form of adult leukaemia.
The project was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Engineering and Physical Sciences Research Council (EPSRC).
A New Platform for Testing Cancer Therapies
The research team used the bone marrow model to analyse the effectiveness and safety of chimeric antigen receptor (CAR) T-cell therapy, an emerging treatment that has already shown promise in several blood cancers. Until now, efforts to apply CAR T-cell therapy to AML have been limited by toxicity to healthy cells and difficulties in predicting how treatments will behave in humans.
To address these challenges, scientists embedded leukaemic hematopoietic stem cells (HSCs) within synthetic peptide hydrogels that mimic the natural bone marrow environment. This approach allowed them to observe how CAR T-cells interact with both cancerous and healthy cells in conditions that more closely resemble those in the human body.
Limitations of Traditional Testing
Studying human HSCs outside the body has long been problematic. Once removed from bone marrow, the cells rapidly change or die, limiting their usefulness in laboratory settings. As a result, many research teams have relied on animal models to test new drugs—an approach that often fails to accurately predict human outcomes.
The University of Glasgow team found that conventional Petri-dish testing methods tended to overestimate the effectiveness of CAR T-cell therapy while failing to reveal its potential harmful effects on healthy cells. The new bioengineered system provided a more accurate picture of therapy performance and potential risks.
Pathway to Improved Treatments
The study also explored the potential of combining CRISPR-Cas9 gene editing with CAR T-cell therapy to selectively target AML cells. Validating this approach has previously been difficult due to differences between human and animal biology. The new model offers a platform to test such combined therapies more reliably before clinical trials.
Dr Hannah Donnelly, research fellow at the University of Glasgow and co-lead author, said the findings highlight a major gap in translating cell therapies from laboratory to clinic. “Conventional, over-simplified testing methods often fail to predict how therapies will behave in humans,” she said. “By using human cells combined with hydrogels to mimic the complex structure of bone marrow, we can detect both therapeutic effects and off-target impacts much earlier.”
Reducing Reliance on Animal Models
The research underscores the potential of non-animal technologies to improve the accuracy of pre-clinical testing and accelerate the development of safer therapies. Professor Anne Ferguson-Smith, Executive Chair of BBSRC, said the work reflects UK Research and Innovation’s commitment to supporting high-impact medical science. “This approach not only accelerates progress towards safer, more effective treatments for acute myeloid leukaemia, but also reflects UKRI’s commitment to supporting cutting-edge research that delivers real-world impact,” she said.
The study, “Synthetic peptide hydrogels as a model of the bone marrow niche demonstrate efficacy of a combined CRISPR–CAR T-cell therapy for acute myeloid leukaemia,” is available in Biomaterials.
