Engineered microtissues for the bystander therapy against cancer

Barbara Blanco-Fernandez, Irene Cano-Torres, Cristina Garrido, Gerard Rubi-Sans, Lourdes Sanchez-Cid, Marta Guerra-Rebollo, Nuria Rubio, Jeronimo Blanco, Soledad Perez-Amodio, Miguel A. Mateos-Timoneda, Elisabeth Engel

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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.

Idioma originalAnglès
Número d’article111854
RevistaMaterials Science and Engineering C
Estat de la publicacióPublicada - de febr. 2021


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