Miniaturized bone marrow-on-a-chip tracks human immune cells as they build lasting antibody defenses

A team of scientists has created a miniature laboratory model that sheds light on the complex journey of antibody-producing plasma cells as they mature and establish themselves within the human bone marrow. This innovative "bone marrow-on-a-chip" platform, which combines a lymph node-mimicking organoid with a tissue chip, allows researchers to observe key stages of plasma cell development that have previously been difficult to study in humans.

The study, published in Science Advances, provides new insights into the function and behavior of plasma cells, which play a crucial role in the immune system by producing antibodies to protect against infections. When antibody production goes awry, plasma cells can contribute to autoimmune diseases, allergies, and even blood cancers.

Understanding how these cells migrate, mature, and survive within the bone marrow is essential for advancing our knowledge of immune system function and developing new therapies for a range of conditions.

The research team, led by Dr. Ankur Singh from Georgia Tech and Dr. Krishnendu Roy from Vanderbilt University, engineered the human lymphoid organoid by isolating B cells from human tonsil tissue and blood sources and growing them in a microenvironment that mimics lymphoid tissue. Meanwhile, Dr. Roy's lab developed a complex microfluidics-based bone marrow chip that closely mimics the conditions found in human bone marrow, including the endosteal and perivascular subniches where plasma cells are stored and activated.

The bone marrow-on-a-chip model is a compact, three-by-five-inch device that replicates the microenvironments of the bone marrow, allowing researchers to study the differentiation and durability of plasma cells in response to signaling proteins. This innovative approach enables high-resolution imaging of plasma cells, providing valuable information about their activity and the effects of various biological niches within the bone marrow on plasma cell development and function.

The researchers note that the model has the potential to be tailored to unique patient populations, allowing them to study the impact of aging on plasma cell function, as well as the development of plasma cells associated with autoimmune or allergic diseases. By providing a more detailed understanding of plasma cell behavior within the bone marrow, this new platform has the potential to advance the development of therapies for immune-related disorders and contribute to the broader understanding of immune system function.