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Human Embryonic Stem Cell-Derived Endothelial Cells as Cellular Delivery Vehicles for Treatment of Metastatic Breast Cancer

Authors :
Weijun Su
Lina Wang
Manqian Zhou
Ze Liu
Shijun Hu
Lingling Tong
Yanhua Liu
Yan Fan
Deling Kong
Yizhou Zheng
Zhongchao Han
Joseph C. Wu
Rong Xiang Ph.D.
Zongjin Li Ph.D.
Source :
Cell Transplantation, Vol 22 (2013)
Publication Year :
2013
Publisher :
SAGE Publishing, 2013.

Abstract

Endothelial progenitor cells (EPCs) have shown tropism towards primary tumors or metastases and are thus potential vehicles for targeting tumor therapy. However, the source of adult EPCs is limited, which highlights the need for a consistent and renewable source of endothelial cells for clinical applications. Here, we investigated the potential of human embryonic stem cell-derived endothelial cells (hESC-ECs) as cellular delivery vehicles for therapy of metastatic breast cancer. In order to provide an initial assessment of the therapeutic potency of hESC-ECs, we treated human breast cancer MDA-MB-231 cells with hESC-EC conditioned medium (EC-CM) in vitro. The results showed that hESC-ECs could suppress the Wnt/β-catenin signaling pathway and thereby inhibit the proliferation and migration of MDA-MB-231 cells. To track and evaluate the possibility of hESC-EC-employed therapy, we employed the bioluminescence imaging (BLI) technology. To study the therapeutic potential of hESC-ECs, we established lung metastasis models by intravenous injection of MDA-MB-231 cells labeled with firefly luciferase (Fluc) and green fluorescent protein (GFP) to NOD/SCID mice. In mice with lung metastases, we injected hESC-ECs armed with herpes simplex virus truncated thymidine kinase (HSV-ttk) intravenously on days 11, 16, 21, and 26 after MDA-MB-231 cell injection. The NOD/SCID mice were subsequently treated with ganciclovir (GCV), and the growth status of tumor was monitored by Fluc imaging. We found that MDA-MB-231 tumors were significantly inhibited by intravenously injected hESC-ECs. The tumor-suppressive effects of the hESC-ECs, by inhibiting Wnt/β-catenin signaling pathway and inducing tumor cell death through bystander effect in human metastatic breast cancer model, provide previously unexplored therapeutic modalities for cancer treatment.

Subjects

Subjects :
Medicine

Details

Language :
English
ISSN :
09636897 and 15553892
Volume :
22
Database :
Directory of Open Access Journals
Journal :
Cell Transplantation
Publication Type :
Academic Journal
Accession number :
edsdoj.76decb158e104843ae662c95982942b1
Document Type :
article
Full Text :
https://doi.org/10.3727/096368912X657927