Open AccessEffects of combined rAAV‐mediated TGF‐β and sox9 gene transfer and overexpression on the metabolic and chondrogenic activities in human bone marrow aspirates
Author(s) -
Tao Ke,
ReyRico Ana,
Frisch Janina,
Venkatesan Jagadeesh Kumar,
Schmitt Gertrud,
Madry Henning,
Lin Jianhao,
Cucchiarini Magali
Publication year - 2017
Publication title -
journal of experimental orthopaedics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 18
ISSN - 2197-1153
DOI - 10.1186/s40634-017-0077-5
Subject(s) - sox9 , chondrogenesis , bone marrow , articular cartilage repair , cartilage , genetic enhancement , transforming growth factor , transplantation , transforming growth factor beta , cancer research , biology , microbiology and biotechnology , immunology , medicine , transcription factor , pathology , osteoarthritis , anatomy , gene , articular cartilage , genetics , alternative medicine
Background Transplantation of genetically modified bone marrow concentrates is an attractive approach to conveniently activate the chondrogenic differentiation processes as a means to improve the intrinsic repair capacities of damaged articular cartilage. Methods Human bone marrow aspirates were co‐transduced with recombinant adeno‐associated virus (rAAV) vectors to overexpress the pleiotropic transformation growth factor beta (TGF‐β) and the cartilage‐specific transcription factor sox9 as a means to enhance the chondroreparative processes in conditions of specific lineage differentiation. Results Successful TGF‐β/ sox9 combined gene transfer and overexpression via rAAV was achieved in chondrogenically induced human bone marrow aspirates for up to 21 days, the longest time point evaluated, leading to increased proliferation, matrix synthesis, and chondrogenic differentiation relative to control treatments (reporter lacZ treatment, absence of vector application) especially when co‐applying the candidate vectors at the highest vector doses tested. Optimal co‐administration of TGF‐β with sox9 also advantageously reduced hypertrophic differentiation in the aspirates. Conclusions These findings report the possibility of directly modifying bone marrow aspirates by combined therapeutic gene transfer as a potent and convenient future approach to improve the repair of articular cartilage lesions.