MP71-19 ESTABLISHING AN EXPERIMENTAL MODEL FOR TARGETING RENAL CELL CARCINOMA USING MESENCHYMAL STEM CELLS IN THE AVIAN CHORIOALLANTOIC MEMBRANE

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I1 Apr 2016MP71-19 ESTABLISHING AN EXPERIMENTAL MODEL FOR TARGETING RENAL CELL CARCINOMA USING MESENCHYMAL STEM CELLS IN THE AVIAN CHORIOALLANTOIC MEMBRANE Zhihao (James) Xu, Hua Chen, Desmond Pink, Katia Carmine-Simmen, John Lewis, and Ronald Moore Zhihao (James) XuZhihao (James) Xu More articles by this author , Hua ChenHua Chen More articles by this author , Desmond PinkDesmond Pink More articles by this author , Katia Carmine-SimmenKatia Carmine-Simmen More articles by this author , John LewisJohn Lewis More articles by this author , and Ronald MooreRonald Moore More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1465AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Metastatic renal cell carcinoma (mRCC) is a lethal urologic disease with 10 year survival less than 5 percent. Recent developments in cell signalling and small molecule therapy for mRCC have impacted progression free survival (PFS) only. High-dose IL-2 immunotherapy can produce durable complete responses (CR) but the response rate is low (16%), highlighting the need for novel therapy. Mesenchymal stem cells (MSCs) have the capacity to mobilize to sites of inflammation. Recently, MSCs were reported to traffic to murine RCC lung metastases via inflammatory signals, opening the potential of delivering tumor site-specific treatment. We hypothesize that human MSCs could target human RCC engrafted in the chorioallantoic membrane (CAM) of the avian embryo. In this project, we investigated potential use of the avian CAM model to study MSC RCC homing. This immunodeficient model is ideal for imaging tumor growth, and cell trafficking. METHODS We first transduced 786-O RCC lines to express green fluorescent protein (GFP), blue fluorescent protein (BFP), or mApple respectively using lentiviral-based vectors. Successful transduction was selected using blasticidin antibiotic treatment. Concurrently, human adipose derived MSCs were isolated from patient perirenal fat, cultured, and characterized using flow cytometry. For the avian CAM model, fluorescent 786-O cells were initially injected into the CAM to establish a viable tumor. The chicken egg vascular endothelium was fluorescently labelled with lectin. MSCs, labelled with a fluorescent plasma membrane stain, were injected IV and observed using intravital imaging via confocal microscopy. RESULTS At 6 weeks post MSC isolation, flow cytometry results indicated that the patient adipose derived primary culture was CD73, CD90, CD105, CD44, CD166 positive and CD45, CD19, CD106, CD146 negative, consistent with MSC expression. All three fluorescent 786-O cell lines were observed by fluorescent microscopy to establish viable and vascularized tumors in the CAM, 7 days post injection. The injected commercial and patient-derived human MSCs were observed to be in proximity to the RCC tumor consistently over periods of 18 hrs and 3 hrs respectively. However, MSCs were not observed to specifically traffic to the RCC tumor. CONCLUSIONS Our results demonstrated that both viable human RCC tumors and human MSCs were established and imaged in the avian CAM model. The stage is set for future studies exploring MSC tumor homing. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e923 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Zhihao (James) Xu More articles by this author Hua Chen More articles by this author Desmond Pink More articles by this author Katia Carmine-Simmen More articles by this author John Lewis More articles by this author Ronald Moore More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...