Tissue Chips for Modeling the Immune System

Understanding the human immune system is key to diagnosing and managing a number of physiological conditions — from wound healing and natural responses to such pathogens as flu viruses to cancer and autoimmune diseases. Furthermore, the immune system’s wound healing and repair processes can be impaired by such diseases as diabetes, which affects more than 30 million people in the United States. Gaining a better understanding of the immune system and its interactions with other physiological systems is a critical research need.

To help address this need, in 2019, the National Institute of Biomedical Imaging and Bioengineering and NCATS funded four research projects focused on developing tissue chips that model components of the human immune system.

The awards are part of the broader Tissue Chip program and were made in response to PAR-19-138.

View the project details below:

Montana State University

Integration of Mononuclear Phagocytes into the Human Gastrointestinal GOFlowChip for Investigation of Luminal Antigen Sampling

Principal Investigators: Seth T. Walk, Ph.D., Diane Bimczok, D.V.M., Ph.D., and James Nolen Wilking, Ph.D.

Grant Number: 1-U01-EB-029242-01

The development of gastrointestinal (GI) organoids during the past five years has revolutionized research in GI development, microbiology and immunology. This project will develop novel in vitro models of the human GI tract to understand its natural responses to microbes and the induction of immune tolerance and activation. The research team seeks to build on its previously developed millimeter-scale fluidic gut-on-a chip platform — the GOFlowChip. The new organoid–microbiome co-culture GOFlowChip system has the potential to become a powerful tool for studies on vaccine or drug delivery and on the impact of intestinal microbiota on antigen sampling.

Learn more about this project in NIH RePORTER.

University of Colorado Denver

A Microphysiological Mimicry of Human Lung–Bone Marrow Organ-Organ Cross-Talk On-a-Chip

Principal Investigator: Kambez Hajipouran Benam, D.Phil.

Grant Number: 1-U01-EB-029085-01

Influenza viruses have a remarkable capacity to evolve and create new strains that can lead to outbreaks, epidemics or pandemics. To mitigate the threat of emerging viruses to public health, rapid and reliable methods are needed to predict their infectivity and virulence. This project aims to develop a novel living multiorgan microsystem that can accurately and quickly predict the pathogenicity of different influenza A viruses by recreating the human lung–bone marrow cross-talk during infection. The organ-on-a-chip platform could accelerate drug development studies by enabling personalized drug efficacy testing and identification of new therapeutic targets.

Learn more about this project in NIH RePORTER.

Massachusetts Institute of Technology

Microvascular Permeability, Inflammation and Lesion Physiology in Endometriosis: A Microphysiological Systems Approach

Principal Investigator: Linda G. Griffith, Ph.D.

Grant Number: 1-U01-EB-029132-01

Endometriosis and adenomyosis are chronic inflammatory diseases that affect tens of millions of women worldwide. Because current drug therapies are inadequate and the animal models used for these diseases are insufficient, this research team proposes using patient samples to build a microphysiological system (MPS) model of early-stage lesions. Three independent MPS platform technologies will be integrated to solve outstanding technical problems in modeling metabolically active tissues. Ultimately, the research team aims to gain quantitative insights into inflammatory cell-cell communication networks in MPS systems.

Learn more about this project in NIH RePORTER.

University of Virginia

A Spatially Organized Microphysiological Model of a Human Lymph Node

Principal Investigator: Rebecca R. Pompano, Ph.D.

Grant Number: 1-U01-EB-029127-01

Organ-on-chip systems to date have excluded the lymph node, a small and highly organized organ that initiates adaptive immune responses. This project will develop the first spatially organized model of the lymph node by combining a three-dimensional culture, microscale patterning and microfluidic technology to mimic the lymph node’s structure, function and dynamics. The researchers aim to produce validated procedures for robust and reproducible assembly of the lymph node chip. In the future, the system can be used in combination with other organ-on-chip systems to model inflammatory and autoimmune diseases, test vaccination strategies and, potentially, test patient-specific immunity.

Learn more about this project in NIH RePORTER