Descrizione del progetto
Una terapia di rigenerazione delle ossa più semplice ed efficace
Le cellule staminali mesenchimali (Mesenchymal Stem Cells, MSC) sono cellule staminali multipotenti capaci di differenziarsi in più tipi cellulari, tra cui osteoblasti e osteociti. Negli ultimi due decenni, la terapia di MSC è stata utilizzata clinicamente per promuovere la guarigione e la rigenerazione ossea. Tuttavia, la sua efficacia dipende da numerosi fattori. Inoltre, le MSC ossee sono raccolte dal midollo osseo di donatori, aggiungendo disagio e complessità al processo. Il progetto EVEREST, finanziato dall’UE, sta cercando di eliminare l’esigenza delle cellule stesse arrivando direttamente alla fonte della loro attività. Le MSC secernono vescicole extracellulari (Extracellular Vesicles, EVs) che trasportano un carico bioattivo. Gli scienziati concentrano la propria attenzione sul chiarire quale componente dell’EV sia fondamentale per la rigenerazione ossea e sul suo sfruttamento per una terapia mirata con EV priva di cellule.
Obiettivo
The therapeutic benefits of mesenchymal stem cells (MSCs), the state-of-the-art treatment for healing bone defects following trauma, resection of cancerous bone tumors, or metabolic bone diseases, has been attributed to their secreted factors. The regenerative potential of MSC-secreted extracellular vesicles (EVs), nanoparticles which deliver bioactive cargo (nucleic acids, proteins, and lipids) between cells, has recently been reported. The applicant will embark upon frontier research with the objective of progressing beyond the state-of-the-art, by harnessing the therapeutic effects of MSCs, but in a cutting-edge, cell-free manner, by developing high potency EV-based bone replacements. This objective will be addressed by firstly testing novel hypotheses to delineate how culture environments, specifically mechanical cues (substrate elasticity and 3D dynamic), hypoxia, and cell stress can modulate the cargo of EVs secreted by MSC. Size exclusion chromatography, which separates EVs from soluble proteins will be employed. Heterogeneity of EV cargo and functionality between human MSC donors will also be evaluated. Answering these hypotheses will permit the intelligent design of targeted EV therapies. The hypothesis that EV-functionalized constructs, fabricated by 3D-printing, will lead to controlled and sustained release of EVs and induce bone formation in vivo will best tested. Together, this will answer critical questions, namely the most favorable environment for collection of potent EVs for regenerative medicine, which secretome component (EV, soluble factors) is responsible for bone regeneration, and whether MSC cell therapy can be replaced by cell-free EVs. EVEREST will develop a platform for targeted EV delivery in ground-breaking, easy to transport and handle, ‘off-the-shelf’ anatomically correct constructs, which have the potential to reduce pain by elimination of bone or bone marrow harvest, and revolutionize the treatment of bone defects.
Campo scientifico
- natural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acids
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesbiological sciencescell biology
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- medical and health sciencesmedical biotechnologycells technologiesstem cells
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-STG - Starting GrantIstituzione ospitante
H91 Galway
Irlanda