Mechanismen von selbstorganisierenden temperatursensitiven Polymeren für verbesserten rAAV-vermittelten Gentransfer in humane mesenchymale Stammzellen

• Antragstellerin: Dr. Ana Rey Rico
• Fachliche Zuordnung: Orthopädie, Unfallchirurgie, rekonstruktive Chirurgie
• Förderung: Förderung von 2015 bis 2018
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 288014206

• Erstellungsjahr: 2018

Zusammenfassung der Projektergebnisse

During the DFG Fellowship we were able to bring evidence of the suitability of the use of PEO-PPO-PEO copolymers as new efficient delivery systems of therapeutic (TGF-β, SOX9) rAAV-2 vectors as an improved means to durably and safely modify hMSCs and human articular chondrocytes relative to free vector treatments with enhanced chondrogenic features relevant of the processes of cartilage repair. This fact highlights the potential of combining adapting tissue engineering platforms to gene transfer approaches mediated by rAAV vectors as an attractive tool to circumvent the natural obstacles from these clinically adapted vectors to achieve an efficient and durable gene expression of the therapeutic sequences within the lesions.

Projektbezogene Publikationen (Auswahl)

• Hydrogel-based controlled delivery systems for articular cartilage repair. Biomed Res Int. 2016, 2016:1215263
  Rey-Rico A, Madry H, Cucchiarini M
  
• PEO-PPO-PEO carriers for rAAV-mediated transduction of human articular chondrocytes in vitro and in a human osteochondral defect model. ACS Appl Mater Interfaces. 2016, 8(32):20600-13
  Rey-Rico A, Frisch J, Venkatesan JK, Schmitt G, Rial-Hermida I, Taboada P, Concheiro A, Madry H, Alvarez-Lorenzo C, Cucchiarini M
  
• rAAV-Mediated Overexpression of TGF-β via vector delivery in polymeric micelles stimulates the biological and reparative activities of human articular chondrocytes in vitro and in a human osteochondral defect model. Int J Nanomedicine. 2017, 12:6985-96
  Rey-Rico A, Venkatesan JK, Schmitt G, Madry H, Concheiro A, Alvarez-Lorenzo C, Cucchiarini M
  
• Supramolecular polypseudorotaxane gels for controlled delivery of rAAV vectors in human mesenchymal stem cells for regenerative medicine. Int J Pharm. 2017, 531(2):492-503
  Rey-Rico A, Babicz H, Madry H, Concheiro A, Alvarez-Lorenzo C, Cucchiarini M