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IBEC Seminar: Prof Marcelle Machluf
viernes, septiembre 13 @ 2:00 pm–4:30 pm
Harnessing the power of stem cell therapy in an off-the-shelf nano-delivery platform for treating brain disorders
Prof Marcelle Machluf, Faculty of Biotechnology and Food Engineering, Technion, Haifa, Israel
Mesenchymal stem cells (MSCs) have gained the most attention in cell therapy, owing to their ability to traverse physiological barriers, and target different sites of inflammation including neurological deseases and primary and metastatic tumors, while exhibiting relative allogeneic safety. However, once transplanted, MSCs undergo changes that alter their targeting capabilities and increase their immunogenicity, only permitting them to exert a short hit-and-run effect. We hypothesised that overcoming these challenges can be realised by combining the safety and inflamatory targeting capabilities of MSCs in an inanimate platform that can withstand limiting host influences. The foundations for this combination are laid by a novel class of nano-vesicles (200 nm), termed nano-ghosts (NGs), equipped with the membrane proteins of MSCs and can be engineered to express additional exogenous ones. The developed -cGMP compliant- technology for the production of NGs from the whole MSC membranes, allow us to load them with a diverse payloads and/or engineer them to express ligands that can combat brain tumors and neuroinflamatory deseas such as MS. Their abundance of natural targeting mechanisms allows the NGs, injected i.v., to bypass the BBB and penetrate the entire tumor bulk or inflamatory site, and rapidly deploy their payload directly into the targeted cells leading to unprecedented tumor growth inhibition and increased animals’ survival in intracranial glioma model. Surprising data also demonstrate that the NGs by themselves can modulate inflammation via cell-cell interaction and significaly reduce MS symtomes in EAE mice without any payload, paving the way for their use in other neuroinflamatory deseas such as Alzhimer and Parkinson. Thus, our results, so far, clearly demonstrate the translational potential of NGs, both as targeted delivery platform as well as a novel immunomodulatory biologic for brain diseass.
