Source: GEN - Genetic Engineering and Biotechnology News, by Uduak Thomas. AI-generated summary by biochip.com, published . Not independently reviewed.
Key takeaways
- Georgia Tech and Vanderbilt created a linked lymphoid organoid and vascularized bone marrow chip for studying human plasma cells.
- The device models endosteal and perivascular bone marrow subniches, which support plasma-cell storage, proliferation and activation.
- The ex vivo model does not establish how faithfully its results predict plasma-cell behavior in living human bone marrow.
Scientists at Georgia Tech and Vanderbilt University have built a bone marrow-on-a-chip system that lets them watch human antibody-producing cells move into, mature within, and persist in a laboratory version of bone marrow. The platform links a human lymphoid organoid, a miniature tissue model that recreates features of a lymph node, with a microfluidic chip designed to reproduce key bone marrow environments. Together, the two components model a major transition in immune biology: B cells become plasma cells and then migrate from lymph nodes, the spleen, and other tissues to bone marrow. Plasma cells are the long-lived immune cells that release antibodies, proteins that recognize microbes and help protect the body during later encounters with an infection. The system gives researchers a way to examine these cells at high imaging resolution without needing to observe them inside living human bone marrow. It also separates two bone marrow subniches, or local cellular neighborhoods, that appear to give plasma cells different signals. The researchers reported the work in Science Advances, with support from the National Institutes of Health. By making a controllable human model of plasma-cell behavior, the chip could help researchers investigate aging, allergy, autoimmunity, and the durability of immune protection.
Building a route from B cell to plasma cell
The project joins expertise from two research groups. Ankur Singh, PhD, professor of bioengineering and director of the Center for Immunoengineering at Georgia Tech, led development of the human lymphoid organoid. Krishnendu Roy, PhD, dean of engineering and professor of biomedical engineering at Vanderbilt University, led the design of the vascularized bone marrow microenvironment.
A lymphoid organoid is a lab-grown tissue system that imitates selected features of an immune organ. Singh's team isolated human B cells from tonsil tissue and blood, then grew them in conditions meant to resemble lymphoid tissue. They used inactivated influenza virus to help address a central culture challenge: encouraging B cells to transform into antibody-secreting plasma cells.
Why the bone marrow destination matters
B cells do not necessarily make antibodies in the same place where they first encounter an infectious threat. Once prepared to become antibody-producing cells, they can leave lymph nodes, the spleen, and other organs and settle in bone marrow. There, some plasma cells can survive for extended periods and continue producing antibodies.
That journey raises an important biological question. A cell's behavior depends not only on its genes but also on its surroundings, much as a seed grows differently in a dry pot than in a well-watered garden. In bone marrow, nearby cells, signaling molecules, structural material, nutrients, and blood vessels can all shape whether plasma cells settle down, multiply, activate, or survive.
A chip with distinct marrow neighborhoods
Roy's group built the bone marrow portion as a microfluidic device, meaning a small engineered platform that guides fluids through tiny channels. The final system fits into a three-by-five stack of 96-well plastic plates, with each plate less than half an inch thick. Its channels are coated with a gel-like material that resembles aspects of bone marrow and includes nutrients and growth factors needed to support plasma-cell function and maintenance.
The chip recreates two distinct locations within bone marrow. One is the endosteal subniche, near the outer edge of the marrow cavity, where plasma cells are stored. The other is the perivascular subniche, deeper in the marrow around blood vessels, where plasma cells proliferate and are activated.
Those locations matter because bone marrow is not one uniform container. It is closer to a city with different districts, each supplying a different mix of resources and instructions. By placing cells in defined marrow-like settings, the researchers can test how individual subniches influence the fate of human antibody-secreting cells.
Seeing cells that are normally hard to observe
Imaging plasma cells in living human bone marrow is exceptionally difficult. Singh noted that researchers can perform some imaging in mouse bone marrow, but those experiments cannot fully capture the behavior of human cells in human tissue conditions. The combined organoid-chip system offers a more accessible way to study human plasma cells while retaining selected structural and biological features of their normal environment.
The model is designed for questions that are hard to isolate in people. Researchers can follow how plasma cells relocate after B-cell activation, examine their interactions with marrow-like regions, and investigate the stop-and-go movement pattern that B cells can show. That pattern may be part of a migration program, but the system provides a setting to test the idea rather than merely infer it from snapshots of cells.
Studying immune memory and immune disease
Long-lived plasma cells are important because they help create immune memory. After an infection or vaccination, persistent antibody production can help the body respond more quickly when it encounters the same pathogen again. The new model could help clarify how bone marrow conditions orient plasma cells and shape their responses during reinfection.
The researchers also envision seeding the device with cells from particular patient groups. Cells from older people could help investigate how aging changes plasma-cell function. Cells from people with autoimmune or allergic diseases could be used to explore how plasma cells that promote autoimmunity or allergy are produced and maintained.
Why This Matters
Immune cells are often studied in flat dishes, where they lack the tissue architecture, fluid flow, and neighboring cells that influence their behavior in the body. Animal models add biological complexity, but they can differ from humans in ways that complicate translation. A human bone marrow-on-a-chip occupies a useful middle ground: it is simplified enough to manipulate and observe, yet structured enough to test how specific marrow environments affect plasma cells.
The system does not replace studies in people or whole animals. Instead, it can help narrow questions before those more difficult experiments begin, such as which local signals help antibody-secreting cells survive, where they migrate, and how disease-associated plasma cells persist. As researchers add patient-derived cells and test additional immune conditions, this platform may become a practical window into the tissue environments that sustain one of the immune system's most important cell types.