title: Ex vivo engineered immune organoids for controlled germinal center reactions.
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 naïve B cells. Compared to existing co-cultures, immune organoids provide a control over primary B cell proliferation with ∼100-fold higher and rapid differentiation to the GC phenotype with robust antibody class switching.
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Purwada
authors.affiliation: Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Manish K
authors.initials: MK
authors.lastname: Jaiswal
authors.affiliation: Division of Hematology and Medical Oncology, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Haelee
authors.initials: H
authors.lastname: Ahn
authors.affiliation: Division of Molecular Biology, Research Institute for Biomedical Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Nojima
authors.affiliation: Division of Molecular Biology, Research Institute for Biomedical Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kitamura
authors.affiliation: Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, USA; Department of Materials Science & Engineering, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Akhilesh K
authors.initials: AK
authors.lastname: Gaharwar
authors.affiliation: Division of Hematology and Medical Oncology, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Leandro
authors.initials: L
authors.lastname: Cerchietti
authors.affiliation: Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY 14853, USA. Electronic address: as2833@cornell.edu.
authors.forename: Ankur
authors.initials: A
authors.lastname: Singh
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D001672:Biocompatible Materials / Q000737:chemistry*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology; D008810:Mice, Inbred C57BL; D053761:Nanocomposites / Q000737:chemistry* / Q000648:ultrastructure; D009924:Organ Culture Techniques / Q000379:methods; D009940:Organoids / Q000166:cytology* / Q000276:immunology; D023822:Tissue Engineering / Q000379:methods
chemical_list: D001672:Biocompatible Materials
keywords: B cell; Class switching; Germinal center; Immuno-engineering; Nanocomposite biomaterials; Organoids