Defects in the microenvironment of the bone marrow, which produces all circulating blood cells, can lead to incurable blood cancers. Few models have been available that faithfully represent the complex functionality and structural features of the human bone marrow, hampering research and drug development processes. Researchers from the University of Oxford and the University of Birmingham have now developed a new method using human stem cells grown in a 3D scaffold to generate all the key components of the human bone marrow.
The senior author of the study, Professor Bethan Psaila, an associate professor of haematology at the Radcliffe Department of Medicine, University of Oxford, said: 'To properly understand how and why blood cancers develop, we need to use experimental systems that closely resemble how real human bone marrow works, which we haven't really had before. It's really exciting to now have this terrific system, as finally, we are able to study cancer directly using cells from our patients, rather than relying on animal models or other simpler systems that do not properly show us how the cancer is developing in the bone marrow in actual patients.'
Publishing their findings in Cancer Discovery, the new bone marrow organoid system faithfully captures the key cellular, molecular and architectural aspects of bone marrow. This life-like architecture enabled the research team to study how the cells in the bone marrow interact to support normal blood cell production, and how this is disturbed in bone marrow fibrosis, where scar tissue builds up in the bone marrow. Bone marrow fibrosis can develop in patients with certain types of blood cancers and remains incurable. The organoid model provides a new avenue for researchers to study this condition and screen potential treatments.
The organoids could further provide insights into different types of blood cancers and bone marrow disorders, such as research into the growth patterns of cancer cells within the marrow. These new organoids can keep cancer cells from blood cancer patients alive in the lab, which proved to be a challenge in the past. This means that researchers may now be able to test customised treatments for specific patients on their own cancer cells, to find the treatments most likely to treat the cancer.
Dr Abdullah Khan, a Sir Henry Wellcome Fellow at the Institute of Cardiovascular Sciences, University of Birmingham, and first author of the study, said: 'Having developed and validated the model is the first crucial step, and in our ongoing collaborative work we will be working with others to better understand how the bone marrow works in healthy people, and what goes wrong when they have blood diseases.'
The researchers hope that this new technique will accelerate the discovery and testing of new personalised blood cancer treatments, improving the clinical translation of novel therapies.