Chondrogenic Differentiation Processes in Human Bone-Marrow Aspirates Seeded in Three-Dimensional-Woven Poly(ɛ-Caprolactone) Scaffolds Enhanced by Recombinant Adeno-Associated Virus–MediatedSOX9Gene Transfer
| Autor: | Jagadeesh K. Venkatesan, Franklin T. Moutos, Farshid Guilak, Janina Frisch, Ana Rey-Rico, Magali Cucchiarini, Gertrud Schmitt, Bradley T. Estes, Henning Madry |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Polyesters Genetic enhancement 02 engineering and technology medicine.disease_cause 03 medical and health sciences Tissue engineering Bone Marrow Genes Reporter Transduction Genetic Genetics medicine Humans Transgenes Progenitor cell Molecular Biology Adeno-associated virus Research Articles Recombination Genetic Tissue Scaffolds Chemistry Cartilage Mesenchymal stem cell Gene Transfer Techniques Cell Differentiation SOX9 Transcription Factor Hypertrophy Dependovirus 021001 nanoscience & nanotechnology Chondrogenesis Cell biology 030104 developmental biology medicine.anatomical_structure Molecular Medicine Bone marrow 0210 nano-technology |
| Zdroj: | Human Gene Therapy. 29:1277-1286 |
| ISSN: | 1557-7422 1043-0342 |
| DOI: | 10.1089/hum.2017.165 |
| Popis: | Combining gene therapy approaches with tissue engineering procedures is an active area of translational research for the effective treatment of articular cartilage lesions, especially to target chondrogenic progenitor cells such as those derived from the bone marrow. This study evaluated the effect of genetically modifying concentrated human mesenchymal stem cells from bone marrow to induce chondrogenesis by recombinant adeno-associated virus (rAAV) vector gene transfer of the sex-determining region Y-type high-mobility group box 9 (SOX9) factor upon seeding in three-dimensional-woven poly(ɛ-caprolactone; PCL) scaffolds that provide mechanical properties mimicking those of native articular cartilage. Prolonged, effective SOX9 expression was reported in the constructs for at least 21 days, the longest time point evaluated, leading to enhanced metabolic and chondrogenic activities relative to the control conditions (reporter lacZ gene transfer or absence of vector treatment) but without affecting the proliferative activities in the samples. The application of the rAAV SOX9 vector also prevented undesirable hypertrophic and terminal differentiation in the seeded concentrates. As bone marrow is readily accessible during surgery, such findings reveal the therapeutic potential of providing rAAV-modified marrow concentrates within three-dimensional-woven PCL scaffolds for repair of focal cartilage lesions. |
| Databáze: | OpenAIRE |
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