Bone Marrow-on-a-Chip Model Offers New Window Into Immune Cell Development and Behavior

With support from the National Institutes of Health, researchers have unveiled a groundbreaking laboratory model that elucidates the migration, maturation, and survival of antibody-producing plasma cells within human bone marrow. This innovative platform integrates a lymph node organoid with a bone marrow tissue chip, facilitating in-depth studies of plasma cell development stages. The findings are detailed in a recent Science Advances publication titled “Ex Vivo Bone Marrow Subniches Influence the Fate of Human Antibody-Secreting Cells.”

The collaborative effort between scientists at Georgia Tech and Vanderbilt University has produced a human lymphoid organoid that closely resembles lymphoid tissue, developed under the leadership of Ankur Singh, PhD. By isolating B cells from human tonsil and blood sources, the team has created an environment conducive to B cell transformation into antibody-secreting plasma cells, utilizing inactivated influenza virus to enhance cell culture challenges.

Simultaneously, Krishnendu Roy, PhD, and his team at Vanderbilt designed a microfluidics-based vascularized environment for the bone marrow chip, replicating the structural and biological functions of human bone marrow. This model, constructed within a compact array of 96-well plates, simulates the endosteal and perivascular subniches critical for plasma cell storage and activation. Singh notes the difficulty of achieving high-resolution imaging of plasma cells in live human bone marrow, a challenge this model seeks to overcome.

This advanced model opens avenues for novel experiments, addressing fundamental questions regarding the relocation of B cells to bone marrow for antibody production and the environmental influences on these cells during reinfection. Furthermore, it allows for the examination of plasma cell functions across diverse patient populations, including those affected by aging, autoimmune disorders, or allergies, potentially revolutionizing our understanding of plasma cell behavior and migration patterns.