Objective:

To create a laboratory model that examines the migration, maturation, and persistence of long-lived antibody-producing plasma cells in human bone marrow.

Approach:

• Model Development: A bone marrow-on-a-chip model was developed by integrating a lymphoid organoid with a tissue chip to replicate bone marrow conditions.
• Cell Culturing: B cells were isolated from human tonsil tissue and blood, cultivated in a microenvironment to mimic lymphoid tissue, and stimulated to differentiate into antibody-secreting plasma cells.
• Microfluidics Engineering: A complex microfluidics-based vascularized microenvironment was engineered to closely mimic human bone marrow conditions.

Key Findings:

• The model allows for observation of critical phases in plasma cell development.
• It enables imaging of plasma cells and their activity in response to signaling proteins.
• The platform can be used to study the effects of aging and diseases on plasma cell function.

Interpretation:

The bone marrow-on-a-chip system provides insights into human immune system function that are not accessible through conventional models.

Limitations:

• Fully reproducing human-body complexity is impossible.
• High-resolution imaging of plasma cells in living human bone marrow is nearly impossible.

Conclusion:

The model offers a novel approach to investigate plasma cell dynamics and could facilitate the study of therapies for infections, allergies, and autoimmunity.

Sources:

• Science Advances
• National Institutes of Health (NIH)