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cc by-nc-nd (c) Elsevier, 2021
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/184321

Engineered microtissues for the bystander therapy against cancer

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Abstract

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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BLANCO FERNÁNDEZ, Bárbara, et al. Engineered microtissues for the bystander therapy against cancer. Materials Science & Engineering C-Materials For Biological Applications. 2021. Vol.  vol 121. ISSN 0928-4931. [consulted: 15 of August of 2026]. Available at: https://hdl.handle.net/2445/184321

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