title: 3D microvascular model recapitulates the diffuse large B-cell lymphoma tumor microenvironment in vitro.
abstract: Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer that affects ∼22 000 people in the United States yearly. Understanding the complex cellular interactions of the tumor microenvironment is critical to the success and development of DLBCL treatment strategies. In vitro platforms that successfully model the complex tumor microenvironment without introducing the variability of in vivo systems are vital for understanding these interactions. To date, no such in vitro model exists that can accurately recapitulate the interactions that occur between immune cells, cancer cells, and endothelial cells in the tumor microenvironment of DLBCL. To that end, we developed a lymphoma-on-chip model consisting of a hydrogel based tumor model traversed by a vascularized, perfusable, round microchannel that successfully recapitulates key complexities and interactions of the in vivo tumor microenvironment in vitro. We have shown that the perfusion capabilities of this technique allow us to study targeted treatment strategies, as well as to model the diffusion of infused reagents spatiotemporally. Furthermore, this model employs a novel fabrication technique that utilizes common laboratory materials, and allows for the microfabrication of multiplex microvascular environments without the need for advanced microfabrication facilities. Through our facile microfabrication process, we are able to achieve micro vessels within a tumor model that are highly reliable and precise over the length of the vessel. Overall, we have developed a tool that enables researchers from many diverse disciplines to study previously inaccessible aspects of the DLBCL tumor microenvironment, with profound implications for drug delivery and design.
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Atlanta, GA, USA. wilbur.lam@emory.edu and The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA and Emory University School of Medicine, Department of Pediatrics, Division of Pediatric Hematology/Oncology, Atlanta, GA, USA and Children's Healthcare of Atlanta, Aflac Cancer & Blood Disorders Center, Atlanta, GA, USA and Institute of Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Robert G
authors.identifier: 0000-0002-7724-7330
authors.initials: RG
authors.lastname: Mannino
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Atlanta, GA, USA. wilbur.lam@emory.edu and The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Adriana N
authors.identifier: 0000-0001-8233-1417
authors.initials: AN
authors.lastname: Santiago-Miranda
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Atlanta, GA, USA. wilbur.lam@emory.edu and The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Pallab
authors.initials: P
authors.lastname: Pradhan
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Atlanta, GA, USA. wilbur.lam@emory.edu and The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA and Emory University School of Medicine, Department of Pediatrics, Division of Pediatric Hematology/Oncology, Atlanta, GA, USA and Children's Healthcare of Atlanta, Aflac Cancer & Blood Disorders Center, Atlanta, GA, USA and Institute of Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Atlanta, GA, USA. wilbur.lam@emory.edu and The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Joscelyn C
authors.initials: JC
authors.lastname: Mejias
authors.affiliation: Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sattva S
authors.initials: SS
authors.lastname: Neelapu
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Atlanta, GA, USA. wilbur.lam@emory.edu and The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Krishnendu
authors.initials: K
authors.lastname: Roy
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Atlanta, GA, USA. wilbur.lam@emory.edu and The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA and Emory University School of Medicine, Department of Pediatrics, Division of Pediatric Hematology/Oncology, Atlanta, GA, USA and Children's Healthcare of Atlanta, Aflac Cancer & Blood Disorders Center, Atlanta, GA, USA and Institute of Electronics and Nanotechnology, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Wilbur A
authors.initials: WA
authors.lastname: Lam
mesh_terms: D000818:Animals; D016403:Lymphoma, Large B-Cell, Diffuse / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D008954:Models, Biological; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment / Q000502:physiology*