ECE2016 Eposter Presentations Thyroid cancer (81 abstracts)
External beam radiation therapy: a promising tool to enhance mesenchymal stem cell migration towards tumors
Christina Schug 1 , Alexandra Wechselberger 2 , Sarah Urnauer 1 , Kathrin A Schmohl 1 , Andrea M Müller 1 , Nathalie Schwenk 1 , Kirsten Lauber 3 , Peter J Nelson 2 & Christine Spitzweg 1
1Department of Internal Medicine II, University Hospital of Munich, Munich, Germany; 2Clinical Biochemistry Group, Medical Poliklinik IV, University Hospital of Munich, Munich, Germany; 3Department of Radiation Oncology, University Hospital of Munich, Munich, Germany.
The tumor-homing property of mesenchymal stem cells (MSC) has led to their use as delivery vehicles for therapeutic genes such as the sodium iodide symporter (NIS), which has convincingly been demonstrated by our recent studies of systemic NIS gene delivery using MSCs as delivery vehicles in both subcutaneous and orthotopic xenograft mouse models. External beam radiation therapy (EBRT) represents a promising tool in the application of engineered MSC (eMSCs)-based gene therapy as tumor irradiation may enhance MSC recruitment into irradiated tumor microenvironments. This effect is presumably mediated through a radiation-induced stimulation of secretion of certain cytokines.
Effects of EBRT on the cytokine secretion profile of human liver cancer cells (HuH7) were investigated by ELISA on supernatants of HuH7 cells, which were irradiated with different doses (1-10 Gy) and removed at intervals from 0–48 h after radiation. Beside an increase in VEGF (up to 1.6-fold) and TSP-1 (up to 2-fold) secretion, a high increase in CXCL12 expression (up to 3-fold) was observed at 48 h post radiation. 48 h supernatants were further tested in a live cell tracking migration assay (IBIDI μ-slides Chemotaxis) monitored by time-lapse microscopy for 24 h. The analysis revealed a profound increase of mean forward migration index (yFMI), mean center of mass (yCoM) and mean directionality of MSCs towards supernatants from irradiated compared to non-irradiated tumor cells implying enhanced MSC migration.
Our data demonstrate that tumor cells secrete higher levels of cytokines and growth factors that are involved in MSC tumor homing after irradiation resulting in stimulation of chemotaxis of MSCs towards tumor cells. This clearly shows the promising potential of EBRT pretreatment to enhance the migratory capacity of MSCs and thus tumor selectivity and therapeutic effectiveness of MSC-mediated gene therapy approaches.
Volume 41
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more