期刊
TISSUE ENGINEERING PART A
卷 21, 期 17-18, 页码 2460-2471出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/ten.tea.2014.0679
关键词
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资金
- German Osteoarthritis Foundation (Deutsche Arthrose-Hilfe e.V.)
- Collaborative Research Partner Acute Cartilage Injury Program of AO Foundation (Davos, Switzerland)
Direct therapeutic gene transfer in marrow concentrates is an attractive strategy to conveniently enhance the chondrogenic differentiation processes as a means to improve the healing response of damaged articular cartilage upon reimplantation in sites of injury. In the present study, we evaluated the ability of the clinically adapted recombinant adeno-associated virus (rAAV) vectors to mediate overexpression of the insulin-like growth factor I (IGF-I) in human bone marrow aspirates that may modulate the proliferative, anabolic activities, and chondrogenic differentiation potential in such samples in vitro. The results demonstrate that successful, significant rAAV-mediated IGF-I gene transfer and expression were achieved in transduced aspirates (up to 105.9 +/- 35.1 pg rhIGF-I/mg total proteins) over time (21 days) at very high levels (similar to 80% of cells expressing the candidate IGF-I transgene), leading to increased levels of proliferation, matrix synthesis, and chondrogenic differentiation over time compared with the control (lacZ) condition. Treatment with the candidate IGF-I vector also stimulated the hypertrophic and osteogenic differentiation processes in the aspirates, suggesting that the regulation of IGF-I expression through rAAV will be a prerequisite for future translation of the approach in vivo. However, these findings show the possible benefits of this vector class to directly modify marrow concentrates as a convenient tool for strategies that aim at improving the repair of articular cartilage lesions.
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