A minimal standardized human bone marrow microphysiological system to assess resident cell behavior during normal and pathological processes

Modeling the human bone marrow (BM) microenvironment is essential for studying hematological diseases and drug responses, yet current models often rely on primary cells that are difficult to standardize or animal models that fail to predict human physiological outcomes. The researchers aimed to create a user-friendly, reproducible, and flexible 3D microphysiological system that mimics the structural and functional complexity of human bone marrow.

To achieve standardization, the team replaced primary stromal cells with the immortalized human HS27A cell line. These cells were cultured on biphasic calcium phosphate (BCP) particles—a scaffold material known to promote rigid bone-like structure formation. The system was designed to be modular, allowing for the independent addition of various cell types, including endothelial cells and hematopoietic progenitors, to study specific cell-cell and cell-matrix interactions. The researchers validated the model by assessing osteoblastic differentiation, extracellular matrix production, and the ability to support hematopoietic stem cell maintenance.

The 3D system successfully generated a well-organized, bone-like structure characterized by the deposition of extracellular matrix components like collagen and fibronectin. The model supported the long-term maintenance of hematopoietic progenitors and allowed for the introduction of pathological elements, such as leukemia cells, which accurately reproduced disease-related changes observed in patient bone marrow. Furthermore, the system is compatible with standard histological imaging and allows for the retrieval of viable cells for functional assays, providing a versatile platform for both basic research and therapeutic testing.

This model offers a significant improvement over existing, highly complex, or heterogeneous systems. By providing a standardized, "minimal" platform that is easier to implement across different laboratories, it facilitates more reliable drug testing and mechanistic studies of bone marrow pathologies, potentially reducing the reliance on animal models that often poorly predict human responses.