Suppression of dedifferentiation and hypertrophy in canine chondrocytes through lentiviral vector expression of Sox9 and induced pluripotency stem cell factors
| Autor: | Peter Young, Padraig Strappe, Saliya Gurusinghe, Jacob Michelsen |
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| Rok vydání: | 2014 |
| Předmět: |
Male
endocrine system Bioengineering Chondrocyte hypertrophy Biology Cell Enlargement Applied Microbiology and Biotechnology Extracellular matrix Chondrocytes Dogs stomatognathic system SOX2 medicine Animals Induced pluripotent stem cell Cells Cultured Cartilage Gene Expression Profiling Lentivirus SOX9 Transcription Factor General Medicine Cell Dedifferentiation musculoskeletal system Chondrogenesis Molecular biology medicine.anatomical_structure Cell culture embryonic structures Stem cell Biotechnology Transcription Factors |
| Zdroj: | Biotechnology letters. 37(7) |
| ISSN: | 1573-6776 |
| Popis: | Prolonged in vitro culture of primary articular chondrocytes results in dedifferentiation to a fibroblast-like cell with reduced expression of the Sox9 transcription factor and the extracellular matrix protein collagen II. The ability to genetically-modify chondrocytes to allow both proliferation and maintenance of an articular phenotype may provide increased numbers of appropriate cells for regeneration of large cartilage defects. Canine chondrocytes were expanded in monolayer culture and transduced with a lentiviral vector expressing Sox9 or in combination with a multicistronic lentiviral vector expressing the four induced pluripotency stem (iPS) cell factors, Oct4, Klf4, Sox2 and c-Myc (OSKM). 3D pellet cultures of transduced cells in the presence of TGFβ-3 revealed increased pellet size and higher levels of total glycosaminoglycan in both Sox9 and Sox9+ OSKM co-transduced chondrocytes compared to untransduced and green fluorescent protein expressing controls. Immunohistochemical detection of Sox9 and collagen II was evident in transduced cells (Sox9, OSKM, or Sox9+ OSKM) with very low levels in untransduced chondrocytes, demonstrating a dedifferentiated state (P |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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