Skip Navigation



Human Molecular Genetics Advance Access published online on December 1, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi438
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
15/2/213    most recent
ddi438v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Gonçalves, M. A.F.V.
Right arrow Articles by Knaän-Shanzer, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gonçalves, M. A.F.V.
Right arrow Articles by Knaän-Shanzer, S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press. All rights reserved
Received September 12, 2005
Accepted November 25, 2005

Article

Human mesenchymal stem cells ectopically expressing full-length dystrophin can complement Duchenne muscular dystrophy myotubes by cell fusion

Manuel A.F.V. Gonçalves 1, Antoine A.F. de Vries 1 *, Maarten Holkers 1, Marloes J.M. van de Watering 1, Ietje van der Velde 1, Gijsbert P. van Nierop 1, Dinko Valerio 1, and Shoshan Knaän-Shanzer 1

1 Department of Molecular Cell Biology, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, the Netherlands

* To whom correspondence should be addressed.
Antoine A.F. de Vries, E-mail: a.a.f.de_vries{at}lumc.nl


  Abstract

Duchenne muscular dystrophy (DMD) is the most prevalent inheritable muscle disease. It is caused by mutations in the ~2.5-megabase dystrophin (Dys)-encoding gene. Therapeutic attempts at DMD have relied on injection of allogeneic Dys-positive myoblasts. The immune rejection of these cells and their limited availability have prompted the search for alternative therapies and sources of myogenic cells. Stem cell-based gene therapy aims to restore tissue function by transplantation of gene-corrected autologous cells. It depends on (i) the capacity of stem cells to participate in tissue regeneration, and (ii) the efficient genetic correction of defective autologous stem cells. We explored the potential of bone marrow-derived human mesenchymal stem cells (hMSCs) genetically modified with the full-length Dys-coding sequence to engage in myogenesis. By tagging hMSCs with enhanced green fluorescent protein (EGFP) or the membrane dye PKH26, we demonstrated that they could participate in myotube formation when cultured together with differentiating human myoblasts. Experiments performed with EGFP-marked hMSCs and DsRed-labeled DMD myoblasts revealed that the EGFP-positive DMD myotubes were also DsRed-positive indicating that hMSCs participate in human myogenesis through cellular fusion. Finally, we showed that hMSCs transduced with a tropism-modified high-capacity hybrid viral vector encoding full-length Dys could complement the genetic defect of DMD myotubes.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Neurol. Neurosurg. PsychiatryHome page
H. Houlden, P. Charlton, and D. Singh
Neurology and orthopaedics
J. Neurol. Neurosurg. Psychiatry, March 1, 2007; 78(3): 224 - 232.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.