2026-04-29T16:56:10Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/176312024-02-08T14:41:51Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927col_20.500.12105_16971

00925njm 22002777a 4500 dc Guerra-Rebollo, Marta author Nogueira de Moraes, Carolina author Alcoholado, Cristina author Soler-Botija, Carolina author Sanchez-Cid, Lourdes author Vila, Olaia F author Meca-Cortés, Oscar author Ramos-Romero, Sara author Rubio, Nuria author Becerra, José author Blanco, Jeronimo author Garrido, Cristina author 2018-09-15 A preclinical model of glioblastoma (GB) bystander cell therapy using human adipose mesenchymal stromal cells (hAMSCs) is used to address the issues of cell availability, quality, and feasibility of tumor cure. We show that a fast proliferating variety of hAMSCs expressing thymidine kinase (TK) has therapeutic capacity equivalent to that of TK-expressing hAMSCs and can be used in a multiple-inoculation procedure to reduce GB tumors to a chronically inhibited state. We also show that up to 25% of unmodified hAMSCs can be tolerated in the therapeutic procedure without reducing efficacy. Moreover, mimicking a clinical situation, tumor debulking previous to cell therapy inhibits GB tumor growth. To understand these striking results at a cellular level, we used a bioluminescence imaging strategy and showed that tumor-implanted therapeutic cells do not proliferate, are unaffected by GCV, and spontaneously decrease to a stable level. Moreover, using the CLARITY procedure for tridimensional visualization of fluorescent cells in transparent brains, we find therapeutic cells forming vascular-like structures that often associate with tumor cells. In vitro experiments show that therapeutic cells exposed to GCV produce cytotoxic extracellular vesicles and suggest that a similar mechanism may be responsible for the in vivo therapeutic effectiveness of TK-expressing hAMSCs. 10.1016/j.omto.2018.09.002 2372-7705 Molecular therapy oncolytics http://hdl.handle.net/10668/13133 30364660 http://hdl.handle.net/20.500.12105/17631 HVS-thymidine kinase Bioluminescence Cell therapy Clarity Extracellular vesicle Glioblastoma bystander therapy in vivo glioblastoma model Mesenchymal stem cell Transparent brain Glioblastoma Bystander Cell Therapy: Improvements in Treatment and Insights into the Therapy Mechanisms.