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Transplanted primary neonatal myoblasts can give rise to functional satellite cells as identified using the Myf5nlacZl+ mouse

Gene Therapy volume 8, pages 778–783 (2001)Cite this article

Abstract

Myoblast transplantation is a potential therapeutic approach for the genetic modification of host skeletal muscle tissue. To be considered an effective, long-lived method of delivery, however, it is essential that at least a proportion of the transplanted cells also retain their proliferative potential. We sought to investigate whether transplanted neonatal myoblasts can contribute to the satellite cell compartment of adult skeletal muscle by using the Myf5nlacZ/+ mouse. The Myf5nlacZ/+ mouse has nlacZ targeted to the Myf5 locus resulting in β-galactosidase activity in quiescent satellite cells. Following transplantation, β-galactosidase-labelled nuclei were detected in host muscles, showing that donor cells had been incorporated. Significantly, β-galactosidase-positive, and therefore donor-derived, satellite cells were detected. When placed in culture, β-galactosidase marked myogenic cells emanated from the parent fibre. These observations demonstrate that cell transplantation not only results in the incorporation of donor nuclei into the host muscle syncytia, but also that the donor cells can become functional satellite cells. The Myf5nlacZ/+ mouse therefore provides a novel and specific marker for determining the contribution of transplanted cells to the satellite cell pool.

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Acknowledgements

This work was supported by EC Contract QLK3-1999-00020, EC Biotechnology Grant BIO4 CT 95–0228 and The British Council/EGIDE Alliance 2000/2001 grant PN 00.172. The Muscle Cell Biology Group was supported by The Medical Research Council, EC Biotechnology Grants BIO4 CT95–0284 and BMH4 CT97–2767. MB's laboratory was supported by grants from the Pasteur Institute, CNRS, Association Française contre les Myopathies and Ministère des Sciences et Technologies. PZ and LH were also supported by the Leopold Muller Foundation and ST by a grant from the HFSPO. We would like to thank Robert Kelly for invaluable help, and Graham Reed and Richard Newton in the MRC CSC Photography department.

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Authors and Affiliations

  1. Muscle Cell Biology Group, Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, UK

    L Heslop, J R Beauchamp, T A Partridge & P S Zammit

  2. Département de Biologie Moléculaire, CNRS URA 1947, Institut Pasteur, Paris, France

    S Tajbakhsh & M E Buckingham

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  1. L Heslop
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  2. J R Beauchamp
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  3. S Tajbakhsh
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  4. M E Buckingham
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  5. T A Partridge
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  6. P S Zammit
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Heslop, L., Beauchamp, J., Tajbakhsh, S. et al. Transplanted primary neonatal myoblasts can give rise to functional satellite cells as identified using the Myf5nlacZl+ mouse. Gene Ther 8, 778–783 (2001). https://doi.org/10.1038/sj.gt.3301463

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