Engineered microtissues for the bystander therapy against cancer

Thymidine kinase expressing human adipose mesenchymal stem cells (TK-hAMSCs) in combination with ganciclovir (GCV) are an effective platform for antitumor bystander therapy in mice models. However, this strategy requires multiple TK-hAMSCs administrations and a substantial number of cells. Therefore...

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Detalles Bibliográficos
Autores: Blanco Fernández, Bárbara|||0000-0001-5050-9663, Cano Torres, Irene, Garrido, Cristina, Rubí Sans, Gerard|||0000-0003-2782-8716, Sanchez Cid, Lourdes, Guerra Rebollo, Marta, Rubio, Nuria, Blanco, Jeronimo, Pérez Amodio, Soledad Graciela|||0000-0001-6825-0194, Mateos Timoneda, Miguel Ángel|||0000-0001-7657-1414, Engel López, Elisabeth|||0000-0003-4855-8874
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/362135
Acceso en línea:https://hdl.handle.net/2117/362135
https://dx.doi.org/10.1016/j.msec.2020.111854
Access Level:acceso abierto
Palabra clave:Stem cells
Cancer--Treatment
Bioluminescence
Tissue engineering
Self-assembled cell-based microtissues
Bystander therapy
Adipose mesenchymal stem cells
Cancer
Cèl·lules mare
Càncer -- Tractament
Bioluminescència
Enginyeria de teixits
Àrees temàtiques de la UPC::Enginyeria biomèdica::Biomaterials
Descripción
Sumario:Thymidine kinase expressing human adipose mesenchymal stem cells (TK-hAMSCs) in combination with ganciclovir (GCV) are an effective platform for antitumor bystander therapy in mice models. However, this strategy requires multiple TK-hAMSCs administrations and a substantial number of cells. Therefore, for clinical translation, it is necessary to find a biocompatible scaffold providing TK-hAMSCs retention in the implantation site against their rapid wash-out. We have developed a microtissue (MT) composed by TKhAMSCs and a scaffold made of polylactic acid microparticles and cell-derived extracellular matrix deposited by hAMSCs. The efficacy of these MTs as vehicles for TK-hAMSCs/GCV bystander therapy was evaluated in a rodent model of human prostate cancer. Subcutaneously implanted MTs were integrated in the surrounding tissue, allowing neovascularization and maintenance of TK-hAMSCs viability. Furthermore, MTs implanted beside tumors allowed TK-hAMSCs migration towards tumor cells and, after GCV administration, inhibited tumor growth. These results indicate that TK-hAMSCs-MTs are promising cell reservoirs for clinical use of therapeutic MSCs in bystander therapies.

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