Display options
Cite
Meng J, Bencze M, Asfahani R, et al. The effect of the muscle environment on the regenerative capacity of human skeletal muscle stem cells. Skelet Muscle. 2015;5:11doi: 10.1186/s13395-015-0036-8.
Meng, J., Bencze, M., Asfahani, R., Muntoni, F., & Morgan, J. E. (2015). The effect of the muscle environment on the regenerative capacity of human skeletal muscle stem cells. Skeletal muscle, 511. https://doi.org/10.1186/s13395-015-0036-8
Meng, Jinhong, et al. "The effect of the muscle environment on the regenerative capacity of human skeletal muscle stem cells." Skeletal muscle vol. 5 (2015): 11. doi: https://doi.org/10.1186/s13395-015-0036-8
Meng J, Bencze M, Asfahani R, Muntoni F, Morgan JE. The effect of the muscle environment on the regenerative capacity of human skeletal muscle stem cells. Skelet Muscle. 2015 Apr 28;5:11. doi: 10.1186/s13395-015-0036-8. eCollection 2015. PMID: 25949786; PMCID: PMC4422426.
Copy Download .nbib Format: NLM
Share it on

Skelet Muscle. 2015 Apr 28;5:11. doi: 10.1186/s13395-015-0036-8. eCollection 2015.

The effect of the muscle environment on the regenerative capacity of human skeletal muscle stem cells.

Skeletal muscle

Jinhong Meng, Maximilien Bencze, Rowan Asfahani, Francesco Muntoni, Jennifer E Morgan

Affiliations

  1. The Dubowitz Neuromuscular Centre, Molecular Neurosciences Section, Developmental Neurosciences Programme, UCL Institute of Child Health, 30 Guilford Street, London, WC1N 1EH UK.

PMID: 25949786 PMCID: PMC4422426 DOI: 10.1186/s13395-015-0036-8

Abstract

BACKGROUND: Muscle stem cell transplantation is a possible treatment for muscular dystrophy. In addition to the intrinsic properties of the stem cells, the local and systemic environment plays an important role in determining the fate of the grafted cells. We therefore investigated the effect of modulating the host muscle environment in different ways (irradiation or cryoinjury or a combination of irradiation and cryoinjury) in two immunodeficient mouse strains (mdx nude and recombinase-activating gene (Rag)2-/γ chain-/C5-) on the regenerative capacity of two types of human skeletal muscle-derived stem cell (pericytes and CD133+ cells).

METHODS: Human skeletal muscle-derived pericytes or CD133+ cells were transplanted into muscles of either mdx nude or recombinase-activating gene (Rag)2-/γ chain-/C5- host mice. Host muscles were modulated prior to donor cell transplantation by either irradiation, or cryoinjury, or a combination of irradiation and cryoinjury. Muscles were analysed four weeks after transplantation, by staining transverse cryostat sections of grafted muscles with antibodies to human lamin A/C, human spectrin, laminin and Pax 7. The number of nuclei and muscle fibres of donor origin and the number of satellite cells of both host and donor origin were quantified.

RESULTS: Within both host strains transplanted intra-muscularly with both donor cell types, there were significantly more nuclei and muscle fibres of donor origin in host muscles that had been modulated by cryoinjury, or irradiation+cryoinjury, than by irradiation alone. Irradiation has no additive effects in further enhancing the transplantation efficiency than cryodamage. Donor pericytes did not give rise to satellite cells. However, using CD133+ cells as donor cells, there were significantly more nuclei, muscle fibres, as well as satellite cells of donor origin in Rag2-/γ chain-/C5- mice than mdx nude mice, when the muscles were injured by either cryodamage or irradiation+cryodamage.

CONCLUSIONS: Rag2-/γ chain-/C5- mice are a better recipient mouse strain than mdx nude mice for human muscle stem cell transplantation. Cryodamage of host muscle is the most effective method to enhance the transplantation efficiency of human skeletal muscle stem cells. This study highlights the importance of modulating the muscle environment in preclinical studies to optimise the efficacy of transplanted stem cells.

Keywords: Animal model; Human skeletal muscle stem cells; Immunodeficiency; Rag2-/γ chain-/C5- mice; Satellite cells; Stem cell therapy; Transplantation; mdx nude mice

References

  1. Nat Cell Biol. 2007 Mar;9(3):255-67 - PubMed
  2. Mol Ther. 2013 Oct;21(10):1950-7 - PubMed
  3. Neuromuscul Disord. 2004 May;14(5):329-36 - PubMed
  4. J Cell Biol. 2000 Mar 6;148(5):985-96 - PubMed
  5. J Physiol. 1997 May 1;500 ( Pt 3):775-85 - PubMed
  6. Int J Exp Pathol. 2014 Dec;95(6):365-77 - PubMed
  7. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2830-4 - PubMed
  8. Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):377-81 - PubMed
  9. Nat Biotechnol. 2007 Sep;25(9):1025-34 - PubMed
  10. Nature. 2008 Nov 27;456(7221):502-6 - PubMed
  11. J Cell Biol. 2002 May 13;157(4):693-702 - PubMed
  12. J Biol Chem. 2002 Dec 6;277(49):47407-11 - PubMed
  13. Hum Gene Ther. 2004 Nov;15(11):1109-24 - PubMed
  14. Neuropathol Appl Neurobiol. 1991 Oct;17(5):353-63 - PubMed
  15. Genes Dev. 2000 Jan 15;14(2):142-6 - PubMed
  16. Cell. 2005 Jul 29;122(2):289-301 - PubMed
  17. Hum Gene Ther. 2001 May 1;12(7):823-31 - PubMed
  18. Nature. 1989 Jan 12;337(6203):176-9 - PubMed
  19. Cell. 1992 Mar 6;68(5):855-67 - PubMed
  20. Cell Transplant. 2005;14(7):457-67 - PubMed
  21. Cell Tissue Res. 1999 Nov;298(2):371-5 - PubMed
  22. Transplantation. 2008 Feb 27;85(4):566-75 - PubMed
  23. Stem Cell Res. 2015 Jan;14(1):20-9 - PubMed
  24. Hum Gene Ther. 2014 Jan;25(1):73-81 - PubMed
  25. J Leukoc Biol. 2009 May;85(5):779-87 - PubMed
  26. PLoS One. 2011 Mar 09;6(3):e17454 - PubMed
  27. Cell Stem Cell. 2007 Dec 13;1(6):646-57 - PubMed
  28. Mol Ther. 2012 Nov;20(11):2168-79 - PubMed
  29. J Cell Biol. 1999 Mar 22;144(6):1113-22 - PubMed
  30. Stem Cells. 2013 Aug;31(8):1611-20 - PubMed
  31. J Cell Sci. 2000 Jun;113 ( Pt 12):2299-308 - PubMed
  32. Mol Ther. 2014 May;22(5):1008-17 - PubMed
  33. Neuromuscul Disord. 2010 Jan;20(1):6-15 - PubMed
  34. Stem Cells. 2012 Sep;30(9):1971-84 - PubMed
  35. J Exp Med. 2007 May 14;204(5):1057-69 - PubMed
  36. PLoS One. 2012;7(5):e37950 - PubMed
  37. J Immunol. 2012 Jun 15;188(12):6267-77 - PubMed
  38. Neuromuscul Disord. 2007 Aug;17(8):631-8 - PubMed
  39. Br J Haematol. 1998 Nov;103(2):335-42 - PubMed
  40. J Cell Sci. 2006 Jul 1;119(Pt 13):2679-87 - PubMed
  41. Stem Cells. 2012 Oct;30(10):2330-41 - PubMed
  42. Mol Ther. 2009 Oct;17 (10 ):1771-8 - PubMed
  43. Acta Pathol Jpn. 1984 Nov;34(6):1221-42 - PubMed

Publication Types

Grant support