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Real-time monitoring of cell transplantation in mouse dystrophic muscles by a secreted alkaline phosphatase reporter gene

Gene Therapy volume 16, pages 815–819 (2009)Cite this article

Abstract

Transplantation of muscle precursor cells (MPCs) is a promising approach for the treatment of muscular dystrophies. However, preclinical and clinical results have shown that the technology is not yet efficient enough for most therapeutic applications. Among the problems that remain unsolved are low cellular survival, poor proliferation and lack of migration of the transplanted cells. One major technical hurdle for the optimization of transplantation protocols is how to follow precisely the fate of the cells after transplantation. In this study, we examined the use of a secreted form of the mouse alkaline phosphatase (mSeAP) enzyme as the reporter system transduced into MPCs using a retroviral vector. We show that circulating mSeAP could be detected in the serum of the transplanted mice at different time points after MPC transplantation. We also found that the level of circulating mSeAP is highly correlated with the number of transplanted cells and that mSeAP is an excellent histological marker. Further, studying the levels of circulating mSeAP compared with the number of muscle fibers positive to mSeAP and to dystrophin, enabled detailed analyses of bottleneck steps for successful transplantation. Taken together, our results show that mSeAP is an excellent quantitative ‘real-time’ reporter gene for cell therapy preclinical studies.

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Acknowledgements

The authors wish to acknowledge the excellent technical help of Simon Jimenez, Christophe Georger and Bernard Gjata from the histology service of Genethon, and to Christel Rivière from the AAV team of Genethon for the gift of recombinant mSeAP.

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Author notes

  1. X Gerard and L Vignaud: These authors contributed equally to this work and should both be regarded as first author.

Authors and Affiliations

  1. FRE3087 CNRS-Genethon, 1 rue de l’Internationale, Evry, France

    X Gerard, L Vignaud, S Charles, D Scherman, A Kichler & D Israeli

  2. Genopole, 4 rue Pierre Fontaine, Evry, France

    C Pinset

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  1. X Gerard
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  2. L Vignaud
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  3. S Charles
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  5. D Scherman
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  6. A Kichler
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  7. D Israeli
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Correspondence to D Israeli.

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Gerard, X., Vignaud, L., Charles, S. et al. Real-time monitoring of cell transplantation in mouse dystrophic muscles by a secreted alkaline phosphatase reporter gene. Gene Ther 16, 815–819 (2009). https://doi.org/10.1038/gt.2009.28

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  • DOI: https://doi.org/10.1038/gt.2009.28

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