Mechanisms of self-assembly temperature-sensitive polymers for enhanced rAAV-mediated gene transfer into human mesenchymal stem cells

• Applicant: Dr. Ana Rey Rico
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2015 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 288014206

• Final Report Year: 2018

Final Report Abstract

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.

Publications

• Hydrogel-based controlled delivery systems for articular cartilage repair. Biomed Res Int. 2016, 2016:1215263
  Rey-Rico A, Madry H, Cucchiarini M
  (See online at https://doi.org/10.1155/2016/1215263)
• 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
  (See online at https://doi.org/10.1021/acsami.6b06509)
• 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
  (See online at https://doi.org/10.2147/IJN.S144579)
• 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
  (See online at https://doi.org/10.1016/j.ijpharm.2017.05.050)