Engineering of a Vascularized 3D Cell Construct On-Chip Using Human iPSC-derived Cells

Friday, 15 November 2019 at 11:00

Add to Calendar ▼2019-11-15 11:00:002019-11-15 12:00:00Europe/LondonEngineering of a Vascularized 3D Cell Construct On-Chip Using Human iPSC-derived CellsMicrofluidics and Organ-on-a-Chip Asia 2019 in Tokyo, JapanTokyo, JapanSELECTBIOenquiries@selectbiosciences.com

Vascular networks are essential to maintain cellular viability and function; however, current 3D culture models lack vascular systems.  Engineering perfusable vascular networks that can deliver reagents and blood cells to 3D cell constructs could be a powerful platform to recapitulate cellular microenvironments and tissue-level functions.  We have developed a microfluidic method to form vascularized tissue-like cell constructs to model cellular interactions through blood vessels.  When a tumor-like cell spheroid containing human umbilical vein endothelial cells (HUVECs) and fibroblasts was cultured in our microfluidic device, a perfusable vascular network was formed through the cancer spheroid.  We confirmed that peripheral blood mononuclear cells can be perfused inside a cancer spheroid through a vascular network.  Thus, we used this system to model the interaction between cancer cells and immune cells.  To study the interaction between cytotoxic T cells and cancer cells thorough blood vessels, allo-reaction between endothelial cells and T cells by mismatching of their HLA will be problematic.  Therefore, we engineered 3D vascular networks using human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs).  CD8+ T cells primed by HUVECs exhibited higher cytotoxic activity toward HUVECs than autologous hiPSC-ECs and MHC class I KO-hiPSC-ECs, demonstrating the potential value of this vascularized cancer-on-a-chip for modeling the interaction between T cells and a tumor-like tissue through blood vessels.  Generation of in vivo-like vascularized 3D cell constructs using hiPSC-ECs would provide a novel platform to develop organs-on-chips as well as human disease models.

Yu-suke Torisawa, Associate Professor, Hakubi Center for Advanced Research, Kyoto University

Yu-suke Torisawa

Yu-suke Torisawa is Associate Professor at the Hakubi Center for Advanced Research and Department of Micro Engineering at Kyoto University. He received his PhD in Chemical Engineering from Tohoku University, Japan in 2006, and conducted postdoctoral studies at the University of Michigan and at the Wyss Institute at Harvard University. His research focuses primarily on developing organ-on-a-chip microdevices including bone marrow, lung, liver, intestine, and cancer models.