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Le Touquet – Paris-Plage, France

Vilquin J.-T.,French Institute of Health and Medical Research | Yada E.,Association Institute of Myology | Catelain C.,Association Institute of Myology
Biomedical and Health Research | Year: 2012

Cell therapy is considered a potential therapeutic avenue for the treatment of skeletal muscle diseases. Heterologous approaches have been attempted in the context of Duchenne muscular dystrophy, a generalized degenerative disease. Cell transplantation trials, however, have been first hampered by the poor survival and the limited migratory ability of the cells, and a first wave of optimizations defined conditions of cell injection and recipient immunosuppression, allowing the achievement of a second set of clinical trials. Further investigations identified anoikis, oxidative stress, fusion inability and some administration methodologies as causes of early massive cell death. New concepts have emerged contemporaneously regarding the correction of gene expression (gene supplementation, exon skipping, gene surgery.), and new myogenic cell types have been identified, mainly in the family of perivascular cells, that can be administered systemically. Then, preclinical models were proposed to adapt the injection strategies, to combine them with genetic modifications of the cells or with pharmacological interventions on the environment to improve the success of implantation. In the meantime, autologous approaches have been attempted in the context of localized repairs. Therefore the continuous identification of new stem cell candidates, the invention of new strategies to restore correct gene expression, the technical and pharmacological improvements of transplantation success, are justified by yet unmet social and medical needs. © 2012 The authors and IOS Press. All rights reserved. Source


Catelain C.,French Institute of Health and Medical Research | Catelain C.,French National Center for Scientific Research | Catelain C.,Association Institute of Myology | Riveron S.,French Institute of Health and Medical Research | And 28 more authors.
Molecular Therapy | Year: 2013

The functional and architectural benefits of embryonic stem cells (ESC) and myoblasts (Mb) transplantations into infarcted myocardium have been investigated extensively. Whereas ESC repopulated fibrotic areas and contributed to myocardial regeneration, Mb exerted their effects through paracrine secretions and scar remodeling. This therapeutic perspective, however, has been less explored in the setting of nonischemic dilated cardiomyopathies (DCMs). Our aim was to compare the integration and functional efficacy of ESC committed to cardiac fate by bone morphogenic protein 2 (BMP-2) pretreatment and Mb used as gold standard following their transplantation into the myocardium of a mouse model of laminopathy exhibiting a progressive and lethal DCM. After 4 and 8 weeks of transplantation, stabilization was observed in Mb-transplanted mice (P = 0.008) but not in groups of ESC-transplanted or medium-injected animals, where the left ventricular fractional shortening (LVFS) decreased by 32 ± 8% and 41 ± 8% respectively. Engrafted differentiated cells were consistently detected in myocardia of mice receiving Mb, whereas few or no cells were detected in the hearts of mice receiving ESC, except in two cases where teratomas were formed. These data suggest that committed ESC fail to integrate in DCM where scar tissue is absent to provide the appropriate niche, whereas the functional benefits of Mb transplantation might extend to nonischemic cardiomyopathy. © The American Society of Gene & Cell Therapy. Source


Vilquin J.-T.,French Institute of Health and Medical Research | Vilquin J.-T.,Association Institute of Myology | Vilquin J.-T.,French National Center for Scientific Research | Catelain C.,French Institute of Health and Medical Research | And 5 more authors.
Current Opinion in Organ Transplantation | Year: 2011

Purpose of review: Cell therapy is considered a potential therapeutic avenue for the treatment of skeletal muscle diseases. Heterologous and autologous approaches have been attempted in the context, respectively, of generalized degenerative disease and of localized repairs. Cell transplantation trials, however, have been hampered by poor survival and limited migratory ability of the cells. This article reviews recent problems including the identification of new putative cellular candidates, the combination of complementary genetic or pharmacological therapeutic approaches, and the set up of clinical trials. Recent findings: Deeper investigations identified anoikis, oxidative stress, fusion inability and some administration methodologies as causes of early massive cell death. It was proposed to adapt the injection strategies or to combine them with genetic modifications of the cells or pharmacological interventions on the environment to improve the success of implantation. New myogenic cell types have been identified, mainly in the family of perivascular cells, which can be administered systemically. New concepts have emerged regarding the correction of gene expression (use of lentiviral vectors, set-up of exon skipping, direct DNA repair, etc.). Summary: Initial cell transplantation trials dedicated to the repair of striated muscles in muscular dystrophies produced mitigated results and underlined some limitations of cellular candidates under study. The research and identification of new stem cell candidates, the invention of new molecular strategies for correction of gene expression, the development of complementary approaches to improve transplantation success, have been justified by the unmet medical needs. These efforts led to new preclinical and clinical trials based on these concepts. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkin. Source

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