Regulated Mesenchymal Stem Cells Mediated Colon Cancer Therapy Assessed by Reporter Gene Based Optical Imaging

摘要: Colorectal cancer is the most common in both men and women second cause of cancer-related deaths. Suicide gene-based therapy with suicide gene-transduced mesenchymal stem cells (MSCs) a promising therapeutic strategy. A tetracycline-controlled Tet-On inducible system used to regulate gene expression may be useful tool for therapies. The aim this study was develop MSCs that induced by an artificial stimulus, validate expression, monitor MSC colon using optical molecular imaging. For our study, we designed retroviral vector developed response plasmid RetroX-TRE (tetracycline element) expressing mutant form herpes simplex virus thymidine kinase (HSV1-sr39TK) dual reporters (eGFP-Fluc2). Bone marrow-derived were transduced RetroX-Tet3G (Clontech, CA, USA) regulatory RetroX-TRE-HSV1-sr39TK-eGFP-IRES-Fluc2, (MSC-Tet-TK/Fluc2 or MSC-Tet-TK) without (MSC-TK/Fluc2 MSC-TK) function. engineered co-cultured (CT26/Rluc) presence prodrug ganciclovir (GCV) after stimulation doxycycline (DOX). Treatment efficiency monitored assessing Rluc Fluc (MSC-Tet-TK activity bystander effect confirmed CT26/Rluc GCV treatment. decreased significantly treatment DOX(+) (p < 0.05 0.01) whereas no significant changes observed DOX(−) cells. In addition, also MSC-Tet-TK cells, but signal MSC-TK confirmed. We assessed xenograft model (CT26/Rluc). successfully HSV1-sr39TK. Our results cancer. provide innovative approach eradicate tumors administration DOX GCV.