Mechanismen von pNaSS-modifizierten Poly(Epsilon)-Caprolactongerüsten für erhöhten rAAV-vermittelten Gentransfer in humanen mesenchymalen Knochenmarkstammzellen
Zusammenfassung der Projektergebnisse
During the DFG Fellowship "Mechanisms of pNaSS-grafted poly(epsilon)-caprolactone scaffolds for enhanced rAAV-mediated gene transfer in human mesenchymal stem cells", the applicant Dr. Jagadeesh K. Venkatesan and his supervisors Profs. Magali Cucchiarini and Henning Madry were able to bring evidence of the suitability of the use of pNaSS-grafted PCL scaffolds as new efficient delivery systems of therapeutic (TGF-β, SOX9) rAAV vectors as an improved means to durably and safely modify human bone marrow aspirates 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)
- Chondrogenic differentiation processes in human bonemarrow aspirates seeded in three-dimensional-woven poly(-caprolactone) scaffolds enhanced by recombinant adeno-associated virus-mediated SOX9 gene transfer. Hum. Gene Ther. 2018, 29(11):1277-86
Venkatesan JK, Moutos FT, Rey-Rico A, Estes BT, Frisch J, Schmitt G, Madry H, Guilak F, Cucchiarini M
(Siehe online unter https://doi.org/10.1089/hum.2017.165) - Controlled release of gene therapy constructs from solid scaffolds for therapeutic applications in orthopedics. Discov. Med. 2018, 25(138):195-203
Venkatesan JK, Falentin-Daudré C, Leroux A, Migonney V, Cucchiarini M
- Biomaterials and gene therapy: a smart combination for MSC musculoskeletal engineering. Curr. Stem Cell Res. Ther. 2019, 14(4):337-43
Mesure B, Menu P, Venkatesan JK, Cucchiarini M, Velot É
(Siehe online unter https://doi.org/10.2174/1574888x14666181205121658) - Current trends in viral gene therapy for human orthopaedic regenerative medicine. Tissue Eng. Regen. Med. 2019, 16(4):345-55
Venkatesan JK, Rey-Rico A, Cucchiarini M.
(Siehe online unter https://doi.org/10.1007/s13770-019-00179-x) - Biomaterial-guided rAAV delivery from pNaSS-grafted PCL films to target human bone marrow aspirates. Tissue Eng. Part A. 2020, 26(7-8):450-9
Venkatesan JK, Falentin-Daudré C, Leroux A, Migonney V, Cucchiarini M.
(Siehe online unter https://doi.org/10.1089/ten.tea.2019.0165) - Enhanced chondrogenic differentiation activities in human bone marrow aspirates via sox9 overexpression mediated by pNaSS-grafted PCL film-guided rAAV gene transfer. Pharmaceutics. 2020, 12(3):280
Venkatesan JK, Meng W, Rey-Rico A, Schmitt G, Speicher-Mentges S, Falentin- Daudré C, Leroux A, Madry H, Migonney V, Cucchiarini M.
(Siehe online unter https://doi.org/10.3390/pharmaceutics12030280) - Scaffold-mediated gene delivery for osteochondral repair. Pharmaceutics. 2020, 12(10):E930
Madry H, Venkatesan JK, Carballo-Pedrares N, Rey-Rico A, Cucchiarini M
(Siehe online unter https://doi.org/10.3390/pharmaceutics12100930)
