Journal
TISSUE ENGINEERING PART A
Volume 21, Issue 17-18, Pages 2460-2471Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/ten.tea.2014.0679
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Funding
- German Osteoarthritis Foundation (Deutsche Arthrose-Hilfe e.V.)
- Collaborative Research Partner Acute Cartilage Injury Program of AO Foundation (Davos, Switzerland)
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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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