Transplanting normal vascular proangiogenic cells to tumor-bearing mice triggers vascular remodeling and reduces hypoxia in tumors.

Cancer Research
Junpei SasajimaYutaka Kohgo

Abstract

Blood vessels deliver oxygen and nutrients to tissues, and vascular networks are spatially organized to meet the metabolic needs for maintaining homeostasis. In contrast, the vasculature of tumors is immature and leaky, resulting in insufficient delivery of nutrients and oxygen. Vasculogenic processes occur normally in adult tissues to repair "injured" blood vessels, leading us to hypothesize that bone marrow mononuclear cells (BMMNC) may be able to restore appropriate vessel function in the tumor vasculature. Culturing BMMNCs in endothelial growth medium resulted in the early outgrowth of spindle-shaped attached cells expressing CD11b/Flt1/Tie2/c-Kit/CXCR4 with proangiogenic activity. Intravenous administration of these cultured vascular proangiogenic cells (VPC) into nude mice bearing pancreatic cancer xenografts and Pdx1-Cre;LSL-Kras(G12D);p53(lox/+) genetically engineered mice that develop pancreatic ductal adenocarcinoma significantly reduced areas of hypoxia without enhancing tumor growth. The resulting vasculature structurally mimicked normal vessels with intensive pericyte coverage. Increases in vascularized areas within VPC-injected xenografts were visualized with an ultrasound diagnostic system during injection of a m...Continue Reading

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Citations

Feb 9, 2012·International Journal of Hematology·Yusuke MizukamiYutaka Kohgo
Sep 5, 2013·International Journal of Hematology·Toru KawamotoYutaka Kohgo
Jul 12, 2011·Physiological Reviews·Shom GoelRakesh K Jain
Jun 13, 2018·Scientific Reports·Yusuke SuzukiMichio Asahi
May 20, 2020·Therapeutic Advances in Medical Oncology·Tianqi SuJiannan Li
Dec 31, 2015·Cancer Discovery·Kyoung Eun LeeM Celeste Simon
Jan 14, 2021·Journal of Hematology & Oncology·Jinxin TaoYupei Zhao

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