Abstract

Models of Lymph Node Function in Top-Down and Bottom-Up Organs-on-Chip

Rebecca Pompano, Assistant Professor, University of Virginia

Predicting the response of the immune system to a new vaccine, a growing tumor, or neurodegenerative disease remains a grand challenge of biomedical science. Standard models of immunity rely largely on in vivo animal studies that are difficult to control and analyze over time, or simple in vitro cultures of human cells that lack the spatial organization and cell-cell interactions of the body. To enable controlled experiments with spatial structure, our laboratory creates spatially organized models of the lymph node and its connections to other organs. This presentation will describe recent work with two approaches. The first approach is “top down”, in which ex vivo slices of lymph node were used to model early responses to vaccination and tumor metastasis. In some cases, we integrated the lymph node slices into user-friendly microfluidic devices to provide environmental control and connectivity.  The second approach is “bottom up,” in which primary human white blood cells were incorporated into a spatially structured organ-on-chip to model the interactions between T cells and B cells that lead to antibody production.  We anticipate that these models of the lymph node are poised for future integration with additional organs and microphysiological systems, and for expansion to reflect the full diversity of the human population.