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Tissue Engineering of Tumor Stromal Microenvironment with Application to Cancer Cell Invasion
Published on: March 18, 2014
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Engineered microtissues for the bystander therapy against cancer
Barbara Blanco-Fernandez1, Irene Cano-Torres2, Cristina Garrido3
1Biomaterials for Regenerative Therapies, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain.
Summary
Engineered microtissues carrying thymidine kinase-expressing mesenchymal stem cells offer a promising scaffold for sustained antitumor bystander therapy, improving cell retention and efficacy in preclinical models.
Area of Science:
- Biomedical Engineering
- Stem Cell Therapy
- Cancer Research
Background:
- Thymidine kinase-expressing human adipose mesenchymal stem cells (TK-hAMSCs) combined with ganciclovir (GCV) show potential for antitumor bystander therapy.
- Current limitations include the need for frequent cell administrations and substantial cell numbers, hindering clinical translation.
- Effective retention of therapeutic cells at the implantation site is crucial for overcoming rapid wash-out.
Purpose of the Study:
- To develop and evaluate a biocompatible scaffold for TK-hAMSCs to enhance retention and efficacy in cancer therapy.
- To assess the therapeutic potential of TK-hAMSCs within a novel microtissue (MT) construct for prostate cancer treatment.
Main Methods:
- Development of a microtissue (MT) composed of TK-hAMSCs and a scaffold of polylactic acid microparticles and cell-derived extracellular matrix.
- Evaluation of MT efficacy in a rodent model of human prostate cancer.
- Assessment of MT integration, cell viability, migration, and tumor growth inhibition after GCV administration.
Main Results:
- Subcutaneously implanted MTs integrated with surrounding tissue, supporting neovascularization and TK-hAMSCs viability.
- MTs facilitated TK-hAMSCs migration towards tumor cells.
- GCV administration following MT implantation inhibited tumor growth, demonstrating therapeutic efficacy.
Conclusions:
- TK-hAMSCs-based microtissues serve as effective cell reservoirs for therapeutic MSCs in bystander therapies.
- This approach shows promise for overcoming limitations of cell retention and improving clinical translation of MSC-based cancer therapies.

