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Enhancement of myogenic and muscle repair capacities of human adipose-derived stem cells with forced expression of MyoD.
Mol Ther. 2009 Jun; 17(6):1064-72.MT

Abstract

Muscle disorders such as Duchenne muscular dystrophy (DMD) still need effective treatments, and mesenchymal stem cells (MSCs) may constitute an attractive cell therapy alternative because they are multipotent and accessible in adult tissues. We have previously shown that human multipotent adipose-derived stem (hMADS) cells were able to restore dystrophin expression in the mdx mouse. The goal of this work was to improve the myogenic potential of hMADS cells and assess the impact on muscle repair. Forced expression of MyoD in vitro strongly induced myogenic differentiation while the adipogenic differentiation was inhibited. Moreover, MyoD-expressing hMADS cells had the capacity to fuse with DMD myoblasts and to restore dystrophin expression. Importantly, transplantation of these modified hMADS cells into injured muscles of immunodepressed Rag2(-/-)gammaC(-/-) mice resulted in a substantial increase in the number of hMADS cell-derived fibers. Our approach combined the easy access of MSCs from adipose tissue, the highly efficient lentiviral transduction of these cells, and the specific improvement of myogenic differentiation through the forced expression of MyoD. Altogether our results highlight the capacity of modified hMADS cells to contribute to muscle repair and their potential to deliver a repairing gene to dystrophic muscles.

Authors+Show Affiliations

Institute of Developmental Biology and Cancer, University of Nice Sophia-Antipolis, CNRS, UMR6543, Nice, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19352326

Citation

Goudenege, Sébastien, et al. "Enhancement of Myogenic and Muscle Repair Capacities of Human Adipose-derived Stem Cells With Forced Expression of MyoD." Molecular Therapy : the Journal of the American Society of Gene Therapy, vol. 17, no. 6, 2009, pp. 1064-72.
Goudenege S, Pisani DF, Wdziekonski B, et al. Enhancement of myogenic and muscle repair capacities of human adipose-derived stem cells with forced expression of MyoD. Mol Ther. 2009;17(6):1064-72.
Goudenege, S., Pisani, D. F., Wdziekonski, B., Di Santo, J. P., Bagnis, C., Dani, C., & Dechesne, C. A. (2009). Enhancement of myogenic and muscle repair capacities of human adipose-derived stem cells with forced expression of MyoD. Molecular Therapy : the Journal of the American Society of Gene Therapy, 17(6), 1064-72. https://doi.org/10.1038/mt.2009.67
Goudenege S, et al. Enhancement of Myogenic and Muscle Repair Capacities of Human Adipose-derived Stem Cells With Forced Expression of MyoD. Mol Ther. 2009;17(6):1064-72. PubMed PMID: 19352326.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhancement of myogenic and muscle repair capacities of human adipose-derived stem cells with forced expression of MyoD. AU - Goudenege,Sébastien, AU - Pisani,Didier F, AU - Wdziekonski,Brigitte, AU - Di Santo,James P, AU - Bagnis,Claude, AU - Dani,Christian, AU - Dechesne,Claude A, Y1 - 2009/04/07/ PY - 2009/4/9/entrez PY - 2009/4/9/pubmed PY - 2009/8/8/medline SP - 1064 EP - 72 JF - Molecular therapy : the journal of the American Society of Gene Therapy JO - Mol. Ther. VL - 17 IS - 6 N2 - Muscle disorders such as Duchenne muscular dystrophy (DMD) still need effective treatments, and mesenchymal stem cells (MSCs) may constitute an attractive cell therapy alternative because they are multipotent and accessible in adult tissues. We have previously shown that human multipotent adipose-derived stem (hMADS) cells were able to restore dystrophin expression in the mdx mouse. The goal of this work was to improve the myogenic potential of hMADS cells and assess the impact on muscle repair. Forced expression of MyoD in vitro strongly induced myogenic differentiation while the adipogenic differentiation was inhibited. Moreover, MyoD-expressing hMADS cells had the capacity to fuse with DMD myoblasts and to restore dystrophin expression. Importantly, transplantation of these modified hMADS cells into injured muscles of immunodepressed Rag2(-/-)gammaC(-/-) mice resulted in a substantial increase in the number of hMADS cell-derived fibers. Our approach combined the easy access of MSCs from adipose tissue, the highly efficient lentiviral transduction of these cells, and the specific improvement of myogenic differentiation through the forced expression of MyoD. Altogether our results highlight the capacity of modified hMADS cells to contribute to muscle repair and their potential to deliver a repairing gene to dystrophic muscles. SN - 1525-0024 UR - https://www.unboundmedicine.com/medline/citation/19352326/Enhancement_of_myogenic_and_muscle_repair_capacities_of_human_adipose_derived_stem_cells_with_forced_expression_of_MyoD_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1525-0016(16)31812-3 DB - PRIME DP - Unbound Medicine ER -