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Multiparametric functional NMR shows alterations associated with plasmid electrotransfer in mouse skeletal muscle.
MedLine Citation:
PMID:  23038159     Owner:  NLM     Status:  Publisher    
BACKGROUND: In vivo gene electrotransfer is frequently used in preclinical gene therapy. Many studies have attempted to optimize protocols efficiency while reducing muscle damage. Most of them reported histological evidence of muscle degeneration and completion of regeneration within 15 days. The functional consequences have rarely been addressed, which may reflect the lack of appropriate techniques. Yet, it is important to characterize the changes induced by the procedure itself, as it may interfere with therapy. We used multiparametric functional (mpf-)NMR to evaluate mice hindlimb muscle after electrotransfer of an empty plasmid. METHODS: NMR experiments were performed in a 4 T Bruker magnet. Arterial spin labeling imaging of perfusion and blood oxygenation level dependent (BOLD) contrast, and (31) P spectroscopy of phosphocreatine kinetics and pH were simultaneously acquired from mice hindlimb during 2 min of electrically stimulated exercise, and recovery. RESULTS: After fifteen days, hindlimb cross-sectional area decreased by 10% compared to controls. Specific force-time integral and end-exercise pH were identical in both groups, while oxidative capacities increased. Perfusion values doubled, and oxygenation significantly decreased. Histology revealed (i) degeneration/regeneration, (ii) decrease in type IIb fibers, (iii) increase in type I and Iia fibers, and (iv) increased capillary density. CONCLUSIONS: In this model, loss in muscle mass was accompanied by important alterations of perfusion and bioenergetics. Fifteen days post-electrotransfer, this was correlated with fiber type shift, capillary bed remodeling, and degeneration/regeneration. Mpf-NMR provides new insights into the functional consequences of standard electrotransfer and constitutes a powerful tool for optimization and longitudinal assessment of preclinical gene therapy protocols. Copyright © 2012 John Wiley & Sons, Ltd.
Celine Baligand; Gregory Jouvion; Olivier Schackman; Helene Gilson; Claire Wary; Jean-Paul Thissen; Pierre G Carlier
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-4
Journal Detail:
Title:  The journal of gene medicine     Volume:  -     ISSN:  1521-2254     ISO Abbreviation:  J Gene Med     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815764     Medline TA:  J Gene Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 John Wiley & Sons, Ltd.
NMR Laboratory, Institute of Myology, F-75651, Paris, France; IdM NMR Laboratory, CEA, I2BM, MIRCen, F-75651, Paris, France; Univ Paris 06, UPMC, F-75005, Paris, France.
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