ComBO: A combined human bone and lympho-myeloid bone marrow organoid for pre-clinical modelling of haematopoietic disorders

We developed a new combined human bone and lympho-myeloid bone marrow organoid (comBO) model using human induced pluripotent stem cells (hiPSCs). To characterise this model, we employed 10x single-cell RNA sequencing (scRNA-seq) to analyze cell composition and cell-cell interactions. Additionally, we engrafted the comBOs with cells derived from healthy donors or multiple myeloma patients and performed scRNA-seq to explore its potential for disease modeling. Overall design: Two approaches were used to generate the comBO model: bulk hydrogel and granular gel. scRNA-seq was applied to both versions for comparative analysis. Subsequently, the fragmented gel method was used to generate comBO organoids engrafted with cells from one healthy donor and three multiple myeloma patients. scRNA-seq was then performed to identify differences in cell composition and interactions across these conditions.