Mesenchymal Stromal Cells (MSC)-derived extracellular vesicles for the delivery of RNAi to modulate angiogenesis in malignancy
• Gabriel A. Monteiro, Professor @ IST/ULisboa, PT
• Cláudia L. da Silva, Professor @ IST/ULisboa, PT
Gene and cell therapy studies continue to advance, aiming at developing novel medicines for a broad range of diseases, including cancer. Angiogenesis is a vital process during tumour development, being a promising target for therapeutic strategies. Recent evidence indicates that mesenchymal stromal cells (MSC) may regulate the tumour microenvironment namely by using the multidirectional communication system established by extracellular vesicles (EVs). Therefore, MSC-derived EVs, featuring low immunogenicity and the ability to cross biological barriers, may constitute a promising vehicle for drug delivery in cancer therapies. In this project, MSC-derived EVs will be modified using direct and indirect methods, through their complementation with RNAi molecules targeting the expression of key players in Vascular Endothelial Growth Factor (VEGF) regulatory pathway. Throughout this work, efforts will focus on developing a well-characterized collection of MSC-derived EVs capable of diminishing angiogenesis in vitro and in vivo, and consequently a promising cell-free cancer therapy.
Ulpiano, C., da Silva, C.L., Monteiro, G.A. Mesenchymal Stromal Cells (MSCs): A Promising Tool for Cell-Based Angiogenic Therapy, Current Gene Therapy, 2021, 21(5), pp. 382 – 405. doi:10.2174/1566523221666210917114353.
Silva, M., Ulpiano, C., Bernardes, N., Monteiro, G.A., da Silva, C.L. Gene delivery as a tool to improve the therapeutic features of mesenchymal stromal cells: methods and applications, in Gene Delivery: Methods and Applications, Zimmer, V. (ed.), Nova Science Publishers, ISBN 9781536162684 (2019)
Ulpiano, C., da Silva, C.L., Monteiro, G.A., Minicircle-derived RNA interference as a novel gene-based anti-angiogenic therapy. In MicroBiotec’21 – Congress of Microbiology and Biotechnology, online virtual format (2021).
Ulpiano, C., Fernandes-Platzgummer, A., da Silva, C.L., Monteiro, G.A., Engineering Extracellular Vesicles from Mesenchymal Stromal Cells using Minicircle-derived RNAi Technology. In 27th ESACT meeting, Lisbon, Portugal (2022).
Ulpiano, C., Fernandes-Platzgummer, A., da Silva, C.L., Monteiro, G.A., Engineering Extracellular Vesicles from Mesenchymal Stromal Cells using Minicircle-derived RNAi Technology. In 12th International Meeting of the SPCE-TC, Braga, Portugal (2021)
Ulpiano, C., da Silva, C.L., Monteiro, G.A., Minicircle-derived RNA interference as a novel gene-based anti-angiogenic therapy. In IST PhD Open Days, Lisboa, Portugal (2021).
Ulpiano, C., da Silva, C.L., Monteiro, G.A.,“RNAi as a tool to inhibit the angiogenic potential of human Mesenchymal Stem/Stromal Cells in malignancy”, MicroBiotec’19 Congress, December 5-7, 2019, Coimbra, Portugal
DOCTORAL PROGRAM (36 ECTS)
• General Doctoral Training (6 ECTS)
• Advanced Experimental Techniques and methodologies (6 ECTS)
• Bioentrepreneurship (6 ECTS)
• Nanobiotechnology (6 ECTS)
• Outreach and Teaching Skills – Department of Bioengineering (6 ECTS)
• Advanced Topics in Bioengineering and Biosciences (6 ECTS)
• Champalimaud Research Symposium 2019 – Tissue Environment in Health and Disease, sponsored by the International Union of Biochemistry and Molecular Biology (IUBMB), October 8-10, 2019, Lisbon, Portugal
• 10th Course on Animal Cell Technology organized by the European Society of Animal Cell Technology, performed in virtual mode, from 21st to 25th September 2020.