A human pathophysiological 3D-bone marrow model reveals immune and stromal cell heterogeneity

Area of Science:

• Hematology
• Cell Biology
• Biotechnology

Background:

• The bone marrow niche is a complex microenvironment critical for hematopoiesis and immune cell function.
• Dysregulated bone marrow niche interactions are implicated in hematological malignancies and cancer metastasis.
• Existing models often fail to fully recapitulate the intricate cellular composition and dynamics of the human bone marrow.

Purpose of the Study:

• To develop and validate a standardized three-dimensional human bone marrow (3D-BOM) model.
• To investigate the behavior of immune and hematopoietic cells within this 3D environment.
• To explore the utility of the 3D-BOM model in studying diseases like acute myeloid leukemia.

Main Methods:

• Establishment of a standardized three-dimensional human bone marrow (3D-BOM) culture system.
• Comparative analysis of immune cell phenotypes in 3D versus 2D cultures.
• Assessment of hematopoietic progenitor cell behavior and stemness maintenance.
• Single-cell transcriptomics to analyze stromal and endothelial cell heterogeneity.
• Evaluation of cellular remodeling in the context of acute myeloid leukemia.

Main Results:

• Monocytes/macrophages exhibited an enhanced pro-inflammatory phenotype in 3D cultures compared to 2D.
• Hematopoietic progenitor cells maintained stemness characteristics over extended serial culture in the 3D niche.
• Single-cell transcriptomics revealed human-like heterogeneity in stromal and endothelial cells.
• Observed remodeling of monocyte/macrophage and endothelial cells in acute myeloid leukemia models within the 3D-BOM.
• The 3D-BOM model successfully recapitulated key features of the human bone marrow microenvironment.

Conclusions:

• The developed 3D-BOM model is a valuable tool for studying human bone marrow physiology and pathology.
• This model provides a more physiologically relevant platform for investigating cellular interactions and disease mechanisms.
• The 3D-BOM facilitates research into hematological malignancies and the bone marrow's role in cancer metastasis.