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Enhanced Adenovirus Transduction of hMSCs Using 3D Hydrogel Cell Carriers

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Abstract

Hydrogels are increasingly being investigated as a means to implant cells for tissue engineering. One way to further enhance the repair response would be to combine the hydrogel cell carrier with gene transfer. Gene therapy, using adenoviral vectors, is an effective way to provide transient delivery of bioactive factors. However, current protocols require further optimization, especially if they are to be transferred into the clinic. This study opted to compare the efficiency of protocols for standard two-dimensional (2D) versus three-dimensional (3D), adenoviral-mediated, transduction of human mesenchymal stem cells. Two different multiplicities of infection were tested. After encapsulation in fibrin, alginate or agarose, cells were cultured for 28 days. Transduction in 3D showed a much higher efficiency, compared to standard 2D transduction protocols. In 3D, the amount of transgene produced was significantly higher, for every condition investigated. Furthermore, transduction in 3D does not require a cell culture step and can be conducted within the operating theatre. In conclusion, it was demonstrated that 3D transduction, using adenoviral vectors, is superior to standard transduction protocols in 2D. It therefore, might help increasing its administration in tissue engineering and clinical applications.

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Acknowledgments

The fibrin used in the experiments was generously supplied by Baxter Biosurgery (Vienna, Austria). This study was supported by Swiss National Fund [SNF 320000-116846/1].

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Authors and Affiliations

  1. Musculoskeletal Regeneration Program, AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos Platz, Switzerland

    Alexander J. Neumann, Mauro Alini & Martin J. Stoddart

  2. Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff, Wales, CF10 3 AX, UK

    Alexander J. Neumann & Charles W. Archer

  3. Orthopedic Surgery Department, Hadassah Hebrew University Medical Center, Kiryat Hadassah 1, 91120, Jerusalem, Israel

    Josh Schroeder

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  1. Alexander J. Neumann
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Correspondence to Martin J. Stoddart.

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Neumann, A.J., Schroeder, J., Alini, M. et al. Enhanced Adenovirus Transduction of hMSCs Using 3D Hydrogel Cell Carriers. Mol Biotechnol 53, 207–216 (2013). https://doi.org/10.1007/s12033-012-9522-y

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