This Notice of Special Interest (NOSI) encourages applications that focus on the development and validation of tissue-, stem-, or progenitor-cell-derived “3D” organotypic culture models (OCM) for transplantation immunology research.
Background
OCM offer several advantages over traditional 2D cell cultures including improved modeling of tissue architecture, cell-cell interactions, and other microenvironmental aspects of tissues and organ systems. To that end, kidney, lung, liver, intestinal, pancreatic islet, spleen, and lymph node organoids are being developed for or are currently used in experimental regenerative medicine applications as well as cancer, autoimmune, and infectious disease research.
Recent developments in OCM are extending the potential utility of these models to investigate complex immunological systems in vitro. Microphysiological systems (MPS) with multiple microfluidic chambers can be used to control differentiation of organoids under mitogen gradients, promote organoid vascularization, and model organ-organ interactions. Technological advancements in biofabrication and 3D printing can generate complex scaffold structures representative of organs with improved reproducibility and scalability. The development of non-immunogenic synthetic or de-cellularized matrices to support organoid formation is another active area of research. This NOSI aims to leverage recent advances in OCM to promote the development of these tools for transplantation immunology research.
Research Objectives
This NOSI will support applications that focus on development of allogeneic or xenogeneic OCM to study immunologic features of transplant-related diseases or conditions, including:
- Cellular rejection, antibody-mediated rejection, or mixed cellular and antibody-mediated rejection
- Sensitization, i.e., immunogenicity of pre-existing allo-reactive or xeno-reactive antibodies
- Tolerance and/or accommodation, i.e., resistance of an organ to immune-mediated damage
- Zoonotic infection in the context of immunosuppression and exposure to a xenograft
- Graft-versus-host disease
- Transplant related ischemia reperfusion injury