title: Angiogenesis in Liquid Tumors: An In Vitro Assay for Leukemic-Cell-Induced Bone Marrow Angiogenesis.
abstract: The critical role of angiogenesis for solid tumor growth and metastatic spread has been well established. In contrast, even though increased vascularity has been commonly observed in bone marrows of patients with hematological malignancies (liquid tumors), the pathophysiology of leukemia-induced angiogenesis in the bone marrow remains elusive. This paper demonstrates the usage of a microengineered 3D biomimetic model to study leukemic-cell-induced bone marrow angiogenesis. Rational design of the 3D angiogenesis chip incorporating endothelial cells (ECs), leukemic cells, and bone marrow stromal fibroblasts provide an efficient biomimetic means to promote and visualize early angiogenic processes. Morphological features of angiogenesis induced by three different leukemic cell lines (U937, HL60, and K562) are investigated and compared. Quantitative measurements of angiogenic factors secreted from monocultures and cocultures of leukemic cells with bone marrow stromal fibroblasts suggest a synergistic relationship between ECs, leukemic cells, and bone marrow stromal fibroblasts for angiogenic induction, and also confirm the necessity of conducting functional angiogenic assays in proper 3D biomimetic cell culture systems like the one developed in this work.
authors.affiliation: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Mechanical and Industrial Engineering, University of Massachusetts, Amherst, MA, 01003, USA.
authors.forename: Yubing
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Applied Physics, University of Science and Technology of China, Anhui, Hefei, 230026, P. R. China.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA.|Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA.
authors.forename: Guohao
authors.initials: G
authors.lastname: Dai
authors.affiliation: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.|Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.|Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Jianping
authors.initials: J
authors.lastname: Fu
mesh_terms: D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D018920:Coculture Techniques; D018922:HL-60 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology; D008954:Models, Biological; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D020298:U937 Cells
keywords: angiogenesis; bone marrow microenvironment; leukemia; microfluidics; organs-on-chips