The development of MDS is closely linked with aging and the body’s inflammatory response. A key observation is that as organisms age, they tend to exhibit a pro-inflammatory state, known as inflammaging, characterized by increased levels of inflammatory markers in cells and tissues. This inflammaging is believed to be a risk factor for MDS, as this persistent inflammatory state creates a conducive environment for the clonal expansion of certain blood cells that had acquired mutations.

Simultaneously, in the bone marrow microenvironment, non-hematopoietic cells also undergo age-related changes, including chromatin restructuring and epigenetic modifications. These alterations, while distinct from the acquired mutations in hematopoietic cells, potentially interact with and exacerbate the inflammaging process. While these inflammatory mechanisms have been extensively studied in mice, their role in humans, particularly at the in vivo or tissue level, remains less explored. Currently, there is a lack of effective tools for studying these complex interactions in aged human bone marrow. To address this gap, we have recently developed a novel human bone marrow organoid derived from induced pluripotent stem cells, which can produce various human blood cells while faithfully replicating the human bone marrow microenvironment. This system will enable us to dissect the age-related molecular and cellular changes leading to bone marrow inflammation at a tissue scale in a human context.