Engineered microtissues for the bystander therapy against cancer
Author
Blanco-Fernandez, Barbara
Cano-Torres, Irene
Garrido, Cristina
Rubi-Sans, Gerardo
Sánchez-Cid, Lourdes
Guerra Rebollo, Marta
Rubio, Nuria
Blanco, Jeronimo
Pérez-Amodio, Soledad
Mateos-Timoneda, Miguel Ángel
Engel, Elisabeth
Other authors
Universitat Ramon Llull. IQS
Publication date
2021-01-13ISSN
0928-4931
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.
Document Type
Article
Document version
Accepted version
Language
English
Subject (CDU)
616 - Pathology. Clinical medicine
Keywords
Self-assembled cell-based microtissues
Bystander therapy
Adipose mesenchymal stem cells
Cancer
Bioluminescence
Càncer
Bioluminescència
Pages
23 p.
Publisher
Elsevier
Is part of
Materials Science and Engineering C
Grant agreement number
info:eu-repo/grantAgreement/EC i ERANET/Centro de Excelencia Severo Ochoa 2016–2019 Program/nAngioderm JTC2018-103
info:eu-repo/grantAgreement/MCIU i TERCEL/PN I+D/MAT2015-68906-R
info:eu-repo/grantAgreement/EC/Grant No.712754
info:eu-repo/grantAgreement/MINECO//PN I+D/Centro de Excelencia Severo Ochoa 2019-2023 Program/SEV-2014-0425
info:eu-repo/grantAgreement/MINECO//PN I+D/Centro de Excelencia Severo Ochoa 2019-2023 Program/CEX2018-000789-S
info:eu-repo/grantAgreement/MINECO//PN I+D/BES-2016-077182
This item appears in the following Collection(s)
Rights
© Elsevier
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-nd/4.0/