Administration of a Soluble Activin Type IIB Receptor Promotes the Transplantation of Human Myoblasts in Dystrophic Mice

Fakhfakh, R.; Lee, Se Jin; Tremblay, Jacques P.

doi:10.3727/096368911x627480

Cited by 14 publications

(14 citation statements)

References 40 publications

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“…. These models also allowed exploring strategies to enhance the transplantation efficacies by quantifying the formation of skeletal muscle fibers of human origin, such as myostatin inhibition (11,12), Wnt3a upregulation (13), or pharmacological treatments (14,15).…”

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confidence: 99%

Modelling human myoblasts survival upon xenotransplantation into immunodeficient mouse muscle

Praud

Vauchez

Zongo

et al. 2018

Experimental Cell Research

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Cell transplantation has been challenged in several clinical indications of genetic or acquired muscular diseases, but therapeutic success were mitigated. To understand and improve the yields of tissue regeneration, we aimed at modelling the fate of CD56-positive human myoblasts after transplantation. Using immunodeficient severe combined immunodeficiency (SCID) mice as recipients, we assessed the survival, integration and satellite cell niche occupancy of human myoblasts by a triple immunohistochemical labelling of laminin, dystrophin and human lamin A/C. The counts were integrated into a classical mathematical decline equation. After injection, human cells were essentially located in the endomysium, then they disappeared progressively from D0 to D28. The final number of integrated human nuclei was grossly determined at D2 after injection, suggesting that no more efficient fusion between donor myoblasts and host fibers occurs after the resolution of the local damages created by needle insertion. Almost 1% of implanted human cells occupied a satellite-like cell niche. Our mathematical model validated by histological counting provided a reliable quantitative estimate of human myoblast survival and/or incorporation into SCID muscle fibers. Informations brought by histological labelling and this mathematical model are complementary.

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confidence: 99%

Modelling human myoblasts survival upon xenotransplantation into immunodeficient mouse muscle

Praud

Vauchez

Zongo

et al. 2018

Experimental Cell Research

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“…The proliferative ability of the hMPCs that survive engraftment may be limited, despite the benefits of iNMES. Growth factors (IGF-1; [ 75 , 77 , 78 ]) or modulatory factors such as the binding site of the ActRIIB receptor, which binds myostatin and other members of the TGF-β family of polypeptide hormones [ 18 ], have been reported to improve engraftment. Although they were tested under different conditions than those used here, they may also promote the growth and differentiation of the grafts formed by hMPCs.…”

Section: Discussionmentioning

confidence: 99%

“…Human myoblasts are often tagged with luciferase [ 13 , 14 ], or green fluorescent protein (GFP) [ 15 , 16 ], to enable them to be tracked by luminometric or fluorescence methods after injection. In some studies, engrafted mice have been exposed to different pharmacological agents, such as Losartan [ 17 ], to alter angiotensin II signaling, or a soluble form of the receptor for myostatin, ActRIIB-Fc [ 18 ], to promote myogenesis and reduce fibrosis. These treatments have improved the survival of the engrafted human myogenic cells in mice and their differentiation into myofibers, but the muscles they form are small and therefore difficult to study by physiological, morphological, and genomic methods.…”

Section: Introductionmentioning

confidence: 99%

“…These treatments have improved the survival of the engrafted human myogenic cells in mice and their differentiation into myofibers, but the muscles they form are small and therefore difficult to study by physiological, morphological, and genomic methods. Moreover, the engrafted muscle tissue may also contain a large number of murine myonuclei, indicating that they are largely hybrid in nature [ 18 – 20 ].…”

Section: Introductionmentioning

confidence: 99%

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Neuromuscular electrical stimulation promotes development in mice of mature human muscle from immortalized human myoblasts

et al. 2015

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BackgroundStudies of the pathogenic mechanisms underlying human myopathies and muscular dystrophies often require animal models, but models of some human diseases are not yet available. Methods to promote the engraftment and development of myogenic cells from individuals with such diseases in mice would accelerate such studies and also provide a useful tool for testing therapeutics. Here, we investigate the ability of immortalized human myogenic precursor cells (hMPCs) to form mature human myofibers following implantation into the hindlimbs of non-obese diabetic-Rag1 null IL2rγ null (NOD-Rag)-immunodeficient mice.ResultsWe report that hindlimbs of NOD-Rag mice that are X-irradiated, treated with cardiotoxin, and then injected with immortalized control hMPCs or hMPCs from an individual with facioscapulohumeral muscular dystrophy (FSHD) develop mature human myofibers. Furthermore, intermittent neuromuscular electrical stimulation (iNMES) of the peroneal nerve of the engrafted limb enhances the development of mature fibers in the grafts formed by both immortal cell lines. With control cells, iNMES increases the number and size of the human myofibers that form and promotes closer fiber-to-fiber packing. The human myofibers in the graft are innervated, fully differentiated, and minimally contaminated with murine myonuclei.ConclusionsOur results indicate that control and FSHD human myofibers can form in mice engrafted with hMPCs and that iNMES enhances engraftment and subsequent development of mature human muscle.

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“…These agents will likely prove beneficial in conjunction with MPC transplantation not only for their ability to stimulate MPC proliferation and differentiation but also for their ability to reduce fibrosis. [69][70][71] MODULATING SIGNALING PATHWAYS. Disruption of the dystrophin scaffold alters key signaling pathways necessary for muscle health and function.…”

Section: Therapeutic Pipeline In 2013mentioning

confidence: 99%

Therapeutic advances in muscular dystrophy

Leung

Wagner

2013

Annals of Neurology

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The muscular dystrophies comprise a heterogeneous group of genetic disorders that produce progressive skeletal muscle weakness and wasting. There has been rapid growth and change in our understanding of these disorders in recent years, and advances in basic science are being translated into increasing numbers of clinical trials. This review will discuss therapeutic developments in 3 of the most common forms of muscular dystrophy: Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, and myotonic dystrophy. Each of these disorders represents a different class of genetic disease (monogenic, epigenetic, and repeat expansion disorders), and the approach to therapy addresses the diverse and complex molecular mechanisms involved in these diseases. The large number of novel pharmacologic agents in development with good biologic rationale and strong proof of concept suggests there will be an improved quality of life for individuals with muscular dystrophy.

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Administration of a Soluble Activin Type IIB Receptor Promotes the Transplantation of Human Myoblasts in Dystrophic Mice

Cited by 14 publications

References 40 publications

Modelling human myoblasts survival upon xenotransplantation into immunodeficient mouse muscle

Modelling human myoblasts survival upon xenotransplantation into immunodeficient mouse muscle

Neuromuscular electrical stimulation promotes development in mice of mature human muscle from immortalized human myoblasts

Therapeutic advances in muscular dystrophy

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