Bioengineered bone marrows that can support stem cells and remodel to mimic human disease metabolism and chemotherapeutic effects

Blood cancer drug discovery is reliant on poorly predictive and costly animal models. Therefore, bioengineered, human cell containing, models are attractive to Pharma. Designing effective bone marrow (BM) models is complicated as they need to both regulate haematopoietic stem cell (HSC) phenotype and be able to undergo remodelling to mimic the blood cancer microenvironment. Here, we develop synthetic hybrid niches using poly(ethylacrylate) to organise laminin on hard, bone mimicking, surfaces and interface with soft, marrow mimicking, polyethylene glycol-fibronectin hydrogels. Optimisation of mesenchymal stromal cell (MSC) mechanobiology within the model offers both support for HSCs and remodelling in response to acute myeloid leukaemia derived cells. The remodelling has many parallels to in vivo and patient data including increased dependency on nestin+ve MSCs, enhanced cytoprotection and increased taurine metabolism. We also use the model to demonstrate, as has been seen in vivo, that targeting taurine enhances effects of chemotherapy.