Article: Purwada, A; Jaiswal, MK; Ahn, H; Nojima, T; Kitamura, D; Gaharwar, AK; Cerchietti, L; Singh, A; (2015) “Ex vivo Engineered Immune Organoids for Controlled Germinal Center Reactions”, Biomaterials, 63:24-34
Abstract: Ex vivo engineered three-dimensional organotypic cultures have enabled the real-time study and control of biological functioning of mammalian tissues. Organs of broad interest where its architectural, cellular, and molecular complexity has prevented progress in ex vivo engineering are the secondary immune organs. Ex vivo immune organs can enable mechanistic understanding of the immune system and more importantly, accelerate the translation of immunotherapies as well as a deeper understanding of the mechanisms that lead to their malignant transformation into a variety of B and T cell malignancies. However, till date, no modular ex vivo immune organ has been developed with an ability to control the rate of immune reaction through tunable design parameter. Here we describe a B cell follicle organoid made of nanocomposite biomaterials, which recapitulates the anatomical microenvironment of a lymphoid tissue that provides the basis to induce an accelerated germinal center (GC) reaction by continuously providing extracellular matrix (ECM) and cell cell signals to naive B cells.
Compared to existing co-cultures, immune organoids provide a control over primary B cell proliferation with similar to 100-fold higher and rapid differentiation to the GC phenotype with robust antibody class switching. (C) 2015 Elsevier Ltd. All rights reserved.
Funding Acknowledgement: National Institutes of Health [1R21CA185236-01]; Cornell University; Weill Cornell Medical College; Howard Hughes Medical Institute [HHMI 56006761]
Funding Text: The authors acknowledge financial support from the National Institutes of Health (1R21CA185236-01), the Cornell University and Weill Cornell Medical College seed grant program, and the Howard Hughes Medical Institute (HHMI 56006761). The authors also thank C. Hernandez, A. August, and R. Weiss at Cornell University for providing animal tissues. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.