Acute myeloid leukaemia (AML) management remains a significant challenge in oncology due to its low survival rates and high post-treatment relapse rates, mainly attributed to treatment-resistant leukaemic stem cells (LSCs) residing in bone marrow (BM) niches. This review offers an in-depth analysis of AML progression, highlighting the pivotal role of extracellular vesicles (EVs) in the dynamic remodelling of BM niche intercellular communication. We explore recent advancements elucidating the mechanisms through which EVs facilitate complex crosstalk, effectively promoting AML hallmarks and drug resistance. Adopting a temporal view, we chart the evolving landscape of EV-mediated interactions within the AML niche, underscoring the transformative potential of these insights for therapeutic intervention. Furthermore, the review discusses the emerging understanding of endothelial cell subsets’ impact across BM niches in shaping AML disease progression, adding another layer of complexity to the disease progression and treatment resistance. We highlight the potential of cutting-edge methodologies, such as organ-on-chip (OoC) and single-EV analysis technologies, to provide unprecedented insights into AML–niche interactions in a human setting. Leveraging accumulated insights into AML EV signalling to reconfigure BM niches and pioneer novel approaches to decipher the EV signalling networks that fuel AML within the human context could revolutionise the development of niche-targeted therapy for leukaemia eradication.

Osteoarthritis (OA) is an inflammatory musculoskeletal disorder that results in cartilage breakdown and alterations in the surrounding tissue microenvironment. Imbalances caused by inflammation and catabolic processes potentiate pathological nerves and blood vessels outgrowth toward damaged areas leading to pain in the patients. Yet, the precise mechanisms leading the nerve sprouting into the aneural cartilaginous tissue remain elusive. In this work, we aim to recapitulate in vitro the hallmarks of OA pathophysiology, including the sensory innervation profile, and provide a sensitive and reliable analytical tool to monitor the in vitro disease progression at microscale. Leveraging the use of patient-derived cells and bioengineering cutting-edge technologies, we engineered cartilage-like microtissues composed of primary human chondrocytes encapsulated in gelatin methacrylate hydrogel. Engineered constructs patterned inside microfluidic devices show the expression of cartilage markers, namely collagen type II, aggrecan, SOX-9 and glycosaminoglycans. Upon pro-inflammatory triggering, using primary human pro-inflammatory macrophage secretome, hallmarks of OA are recapitulated namely catabolic processes of human chondrocytes and the sensory innervation profile, supported by gene expression and functional assays. To monitor the OA micropathological system, a highly sensitive technology - EliChip™ - is presented to quantitively assess the molecular signature of cytokines and growth factors (interleukin 6 and nerve growth factor) produced from a single microfluidic chip. Herein, we report a miniaturized pathophysiological model and analytical tool to foster the neuro-immune interactions playing a role in cartilage-related disorders.