TY - JOUR
T1 - State of art and limitations in genetic engineering to induce stable chondrogenic phenotype
AU - Graceffa, Valeria
AU - Vinatier, Claire
AU - Guicheux, Jerome
AU - Evans, Christopher H.
AU - Stoddart, Martin
AU - Alini, Mauro
AU - Zeugolis, Dimitrios I.
N1 - Funding Information:
The authors would like to acknowledge for financial support: Science Foundation Ireland /European Regional Development Fund (Grant Agreement Number: 13/RC/2073 ); Science Foundation Ireland , Career Development Award (Grant Agreement Number: 15/CDA/3629 ); H2020, Marie Skłodowska-Curie Actions, Innovative Training Networks 2015 Tendon Therapy Train project (Grant Agreement Number: 676338 ); the French network ‘ROAD’ from the Arthritis Foundation ; and the French Society of Rheumatology (Grant Agreement Numbers: 3637 and 4015 ).
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/11/15
Y1 - 2018/11/15
N2 - Current protocols for chondrocyte expansion and chondrogenic differentiation of stem cells fail to reduce phenotypic loss and to mitigate hypertrophic tendency. To this end, cell genetic manipulation is gaining pace as a means of generating cells with stable chondrocyte phenotype. Herein, we provide an overview of candidate genes that either induce cartilage regeneration or inhibit cartilage degeneration. We further discuss in vitro, ex vivo and in vivo viral transduction and non-viral transfection strategies for targeted cells (chondrocytes, mesenchymal stem cells, induced pluripotent stem cells and synovial cells), along with the most representative results obtained in pre-clinical models and in clinical trials. We highlight current challenges and associated risks that slowdown clinical acceptance and commercialisation of gene transfer technologies.
AB - Current protocols for chondrocyte expansion and chondrogenic differentiation of stem cells fail to reduce phenotypic loss and to mitigate hypertrophic tendency. To this end, cell genetic manipulation is gaining pace as a means of generating cells with stable chondrocyte phenotype. Herein, we provide an overview of candidate genes that either induce cartilage regeneration or inhibit cartilage degeneration. We further discuss in vitro, ex vivo and in vivo viral transduction and non-viral transfection strategies for targeted cells (chondrocytes, mesenchymal stem cells, induced pluripotent stem cells and synovial cells), along with the most representative results obtained in pre-clinical models and in clinical trials. We highlight current challenges and associated risks that slowdown clinical acceptance and commercialisation of gene transfer technologies.
KW - Cartilage tissue engineering
KW - Gene engineering
KW - Genetically engineered cells
KW - Non-viral transfection systems
KW - Viral transduction systems
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U2 - 10.1016/j.biotechadv.2018.07.004
DO - 10.1016/j.biotechadv.2018.07.004
M3 - Review article
C2 - 30012541
AN - SCOPUS:85050091939
VL - 36
SP - 1855
EP - 1869
JO - Biotechnology Advances
JF - Biotechnology Advances
SN - 0734-9750
IS - 7
ER -