State of art and limitations in genetic engineering to induce stable chondrogenic phenotype |
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| Authors: | Valeria Graceffa Claire Vinatier Jerome Guicheux Christopher H Evans Martin Stoddart Mauro Alini Dimitrios I Zeugolis |
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| Institution: | 1. Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway), Galway, Ireland;2. Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway), Galway, Ireland;3. INSERM, UMR 1229-RMeS, Regenerative Medicine and Skeleton, Team STEP, 44042 Nantes, France;4. Nantes University, School of Dental Medicine, 44042 Nantes, France;5. CHU Nantes, PHU 4 OTONN, 44042 Nantes, France;6. Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN, United States;g. AO Research Institute, Davos, Switzerland |
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| Abstract: | 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. |
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| Keywords: | Gene engineering Cartilage tissue engineering Viral transduction systems Non-viral transfection systems Genetically engineered cells |
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