An artificial blood vessel implanted three-dimensional microsystem for modeling transvascular migration of tumor cells.

Reproducing a tumor microenvironment consisting of blood vessels and tumor cells for modeling tumor invasion in vitro is particularly challenging. Here, we report an artificial blood vessel implanted 3D microfluidic system for reproducing transvascular migration of tumor cells. The transparent, porous and elastic artificial blood vessels are obtained by constructing polysaccharide cellulose-based microtubes using a chitosan sacrificial template, and possess excellent cytocompatibility, permeability, and mechanical characteristics. The artificial blood vessels are then fully implanted into the collagen matrix to reconstruct the 3D microsystem for modeling transvascular migration of tumor cells. Well-defined simulated vascular lumens were obtained by proliferation of the human umbilical vein endothelial cells (HUVECs) lining the artificial blood vessels, which enables us to reproduce structures and functions of blood vessels and replicate various hemodynamic parameters. Based on this model, the adhesion and transvascular migration of tumor cells across the artificial blood vessel have been well reproduced.

[1]  Ali Khademhosseini,et al.  SAM-based cell transfer to photopatterned hydrogels for microengineering vascular-like structures. , 2011, Biomaterials.

[2]  David L Kaplan,et al.  Silk fibroin microtubes for blood vessel engineering. , 2007, Biomaterials.

[3]  Yong-Gon Koh,et al.  Trends in Tissue Engineering for Blood Vessels , 2012, Journal of biomedicine & biotechnology.

[4]  C. Doillon,et al.  Preparation of ready-to-use, storable and reconstituted type I collagen from rat tail tendon for tissue engineering applications , 2006, Nature Protocols.

[5]  B. le Bail,et al.  Human hepatic myofibroblasts increase invasiveness of hepatocellular carcinoma cells: Evidence for a role of hepatocyte growth factor , 1997, Hepatology.

[6]  Roger D Kamm,et al.  Sprouting angiogenesis under a chemical gradient regulated by interactions with an endothelial monolayer in a microfluidic platform. , 2011, Analytical chemistry.

[7]  Brendon M. Baker,et al.  Rapid casting of patterned vascular networks for perfusable engineered 3D tissues , 2012, Nature materials.

[8]  Lina Zhang,et al.  Swelling Behaviors of pH- and Salt-Responsive Cellulose-Based Hydrogels , 2011 .

[9]  Lina Zhang,et al.  Fabrication and characterization of novel macroporous cellulose–alginate hydrogels , 2009 .

[10]  Craig A Simmons,et al.  Macro- and microscale fluid flow systems for endothelial cell biology. , 2010, Lab on a chip.

[11]  Lauren L Bischel,et al.  Tubeless microfluidic angiogenesis assay with three-dimensional endothelial-lined microvessels. , 2013, Biomaterials.

[12]  Nigel C Bird,et al.  The role of cell adhesion molecules in the progression of colorectal cancer and the development of liver metastasis. , 2009, Cellular signalling.

[13]  P. Carmeliet,et al.  Modeling lymphangiogenesis in a three-dimensional culture system , 2008, Nature Methods.

[14]  I. Macdonald,et al.  Clinical targets for anti-metastasis therapy. , 2000, Advances in cancer research.

[15]  S. Williams,et al.  Dynamic measurement of human capillary blood pressure. , 1988, Clinical science.

[16]  P. Carmeliet,et al.  Angiogenesis in cancer and other diseases , 2000, Nature.

[17]  P. Chu,et al.  Vascular lumen simulation and highly-sensitive nitric oxide detection using three-dimensional gelatin chip coupled to TiC/C nanowire arrays microelectrode. , 2012, Lab on a chip.

[18]  G. Colditz,et al.  Prostate cancer: is it time to expand the research focus to early-life exposures? , 2013, Nature Reviews Cancer.

[19]  Lina Zhang,et al.  Rapid dissolution of cellulose in LiOH/urea and NaOH/urea aqueous solutions. , 2005, Macromolecular bioscience.

[20]  Jianhua Qin,et al.  A microfluidic-based device for study of transendothelial invasion of tumor aggregates in realtime. , 2012, Lab on a chip.

[21]  J. Segall,et al.  Intravital imaging of cell movement in tumours , 2003, Nature Reviews Cancer.

[22]  J. Rubin,et al.  Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. , 1991, Science.

[23]  J. Quigley,et al.  Tumor Cell Intravasation Alu-cidated The Chick Embryo Opens the Window , 1998, Cell.

[24]  Lina Zhang,et al.  Effects of coagulants on porous structure of membranes prepared from cellulose in NaOH/urea aqueous solution , 2006 .

[25]  K. Alitalo,et al.  VEGF and angiopoietin signaling in tumor angiogenesis and metastasis. , 2011, Trends in molecular medicine.

[26]  S. Morrison,et al.  Human Melanoma Metastasis in NSG Mice Correlates with Clinical Outcome in Patients , 2012, Science Translational Medicine.

[27]  N. L'Heureux,et al.  Human tissue-engineered blood vessels for adult arterial revascularization , 2007, Nature Medicine.

[28]  Ali Khademhosseini,et al.  Functional Human Vascular Network Generated in Photocrosslinkable Gelatin Methacrylate Hydrogels , 2012, Advanced functional materials.

[29]  R. Kamm,et al.  Three-dimensional microfluidic model for tumor cell intravasation and endothelial barrier function , 2012, Proceedings of the National Academy of Sciences.

[30]  G. Giridharan,et al.  Endothelial cell culture model for replication of physiological profiles of pressure, flow, stretch, and shear stress in vitro. , 2011, Analytical chemistry.

[31]  C. Webb,et al.  Hepatocyte growth factor expression in human cancer and therapy with specific inhibitors. , 2001, Anticancer research.

[32]  D. Spandidos,et al.  Expression of miRNAs involved in angiogenesis, tumor cell proliferation, tumor suppressor inhibition, epithelial-mesenchymal transition and activation of metastasis in bladder cancer. , 2012, The Journal of urology.

[33]  Lina Zhang,et al.  Novel regenerated cellulose films prepared by coagulating with water: Structure and properties. , 2012, Carbohydrate polymers.

[34]  Wei Zhang,et al.  A Strategy for Depositing Different Types of Cells in Three Dimensions to Mimic Tubular Structures in Tissues , 2012, Advanced materials.

[35]  Xingyu Jiang,et al.  Engineering a 3D vascular network in hydrogel for mimicking a nephron. , 2013, Lab on a chip.

[36]  D. Kass,et al.  In vitro system to study realistic pulsatile flow and stretch signaling in cultured vascular cells. , 2000, American journal of physiology. Cell physiology.

[37]  Hyungil Jung,et al.  Integration of intra- and extravasation in one cell-based microfluidic chip for the study of cancer metastasis. , 2011, Lab on a chip.

[38]  Yuhong Pang,et al.  Quantitative study of the dynamic tumor-endothelial cell interactions through an integrated microfluidic coculture system. , 2012, Analytical chemistry.

[39]  Palaniappan Sethu,et al.  Microfluidic cardiac cell culture model (μCCCM). , 2010, Analytical chemistry.

[40]  I. Fidler,et al.  The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited , 2003, Nature Reviews Cancer.

[41]  F. Orr,et al.  Intravital videomicroscopic evidence for regulation of metastasis by the hepatic microvasculature: effects of interleukin-1alpha on metastasis and the location of B16F1 melanoma cell arrest. , 1997, Cancer research.

[42]  Milica Radisic,et al.  Perfusable branching microvessel bed for vascularization of engineered tissues , 2012, Proceedings of the National Academy of Sciences.

[43]  Ying Zheng,et al.  In vitro microvessels for the study of angiogenesis and thrombosis , 2012, Proceedings of the National Academy of Sciences.

[44]  Russell Hughes,et al.  Current methods for assaying angiogenesis in vitro and in vivo , 2004, International journal of experimental pathology.

[45]  Pan Liu,et al.  Cellulose-based hydrogels with excellent microstructural replication ability and cytocompatibility for microfluidic devices , 2013, Cellulose.