Multipotential Mesoangioblast Stem Cell Therapy in the
            <i>
              Mdx/Utrn
              <sup>-/-</sup>
            </i>
            mouse model for Duchenne muscular dystrophy

Berry, Suzanne E.; Liu, Jianming; Chaney, Eric J.; Kaufman, Stephen J.

doi:10.2217/17460751.2.3.275

Cited by 65 publications

(57 citation statements)

References 60 publications

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“…Interestingly, this contribution to the regenerated fibers, delayed with regard to the systemic delivery, could promote ongoing repair of dystrophic muscle. 85 Recently, a marked improvement of muscle performance was measured in both respiratory and cardiac muscles of mdx mice following treatment with halofuginone, a collagen synthesis inhibitor that prevented fibrosis. 86,87 By demonstrating the key role of fibrosis on muscle function alterations in a dystrophic context, these findings support the hypothesis that the major restriction in endomysial expansion observed in the muscles of our treated GRMD dogs might have a direct impact on their walking ability and largely contribute to their clinical stabilization.…”

Section: Discussionmentioning

confidence: 99%

Systemic Delivery of Allogenic Muscle Stem Cells Induces Long-Term Muscle Repair and Clinical Efficacy in Duchenne Muscular Dystrophy Dogs

Rouger

Larcher

Dubreil

et al. 2011

The American Journal of Pathology

100

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Duchenne muscular dystrophy (DMD) is a genetic progressive muscle disease resulting from the lack of dystrophin and without effective treatment. Adult stem cell populations have given new impetus to cellbased therapy of neuromuscular diseases. One of them, muscle-derived stem cells, isolated based on delayed adhesion properties, contributes to injured muscle repair. However, these data were collected in dystrophic mice that exhibit a relatively mild tissue phenotype and clinical features of DMD patients. Here, we characterized canine delayed adherent stem cells and investigated the efficacy of their systemic delivery in the clinically relevant DMD animal model to assess potential therapeutic application in humans. Delayed adherent stem cells, named MuStem cells (muscle stem cells), were isolated from healthy dog muscle using a preplating technique. In vitro, MuStem cells displayed a large expansion capacity, an ability to proliferate in suspension, and a multilineage differentiation potential. Phenotypically, they corresponded to early myogenic progenitors and uncommitted cells. When injected in immunosuppressed dystrophic dogs, they contributed to myofiber regeneration, satellite cell replenishment, and dystrophin expression. Importantly, their systemic delivery resulted in long-term dystrophin expression, muscle damage course limitation with an increased regeneration activity and an interstitial expansion restriction, and persisting stabilization of the dog's clinical status. These results demonstrate that MuStem cells could provide an attractive therapeutic avenue for DMD patients.

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Section: Discussionmentioning

confidence: 99%

Systemic Delivery of Allogenic Muscle Stem Cells Induces Long-Term Muscle Repair and Clinical Efficacy in Duchenne Muscular Dystrophy Dogs

Rouger

Larcher

Dubreil

et al. 2011

The American Journal of Pathology

100

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“…The mdx/utrn Ϫ/Ϫ mice lacking dystrophin and utrophin exhibit progressive muscular dystrophy, markedly reduced mobility and life span, and severe abnormalities at the neuromuscular and myotendinous junctions (20,30). Since the pathology of skeletal and cardiac muscle of mdx/utrn Ϫ/Ϫ mice more closely resembles that in DMD patients than the pathology of mdx mice, the doubly deficient mouse is a useful and appropriate model for developing and testing new therapies for muscular dystrophy (4,12,13,27,31).In addition to increased utrophin expression, DMD patients and mdx mice also have more ␣ 7 ␤ 1 -integrin (36, 74). Other cytoskeleton-associated proteins in integrin focal adhesions, such as vinculin and talin, are also elevated in mdx mice (44).…”

mentioning

confidence: 99%

Increasing α₇β₁-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression

Liu

Burkin²,

Kaufman

2008

American Journal of Physiology-Cell Physiology

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Liu J, Burkin DJ, Kaufman SJ. Increasing ␣7␤1-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression. Am J Physiol Cell Physiol 294: C627-C640, 2008. First published November 28, 2007 doi:10.1152/ajpcell.00329.2007.-The dystrophin-glycoprotein complex maintains the integrity of skeletal muscle by associating laminin in the extracellular matrix with the actin cytoskeleton. Several human muscular dystrophies arise from defects in the components of this complex. The ␣ 7␤1-integrin also binds laminin and links the extracellular matrix with the cytoskeleton. Enhancement of ␣ 7-integrin levels alleviates pathology in mdx/utrn Ϫ/Ϫ mice, a model of Duchenne muscular dystrophy, and thus the integrin may functionally compensate for the absence of dystrophin. To test whether increasing ␣ 7-integrin levels affects transcription and cellular functions, we generated ␣ 7-integrin-inducible C2C12 cells and transgenic mice that overexpress the integrin in skeletal muscle. C2C12 myoblasts with elevated levels of integrin exhibited increased adhesion to laminin, faster proliferation when serum was limited, resistance to staurosporine-induced apoptosis, and normal differentiation. Transgenic expression of eightfold more integrin in skeletal muscle did not result in notable toxic effects in vivo. Moreover, high levels of ␣ 7-integrin in both myoblasts and in skeletal muscle did not disrupt global gene expression profiles. Thus increasing integrin levels can compensate for defects in the extracellular matrix and cytoskeleton linkage caused by compromises in the dystrophin-glycoprotein complex without triggering apparent overt negative side effects. These results support the use of integrin enhancement as a therapy for muscular dystrophy. myoblast proliferation; integrin transgenic mice; microarray CELLS CAN RECOGNIZE AND INTERACT with their environment through membrane receptors specific for different extracellular matrix proteins. The heterodimeric integrins are evolutionarily conserved receptors for matrix proteins found in all metazoans (37). In skeletal muscle, the association of the extracellular matrix with the cytoskeleton is essential for maintaining the integrity of the sarcolemma, sustaining appropriate myofiber architecture, and correctly transmitting the forces produced by muscle contractions (5, 42). The ␣ 7 ␤ 1 -integrin is part of a linkage system that maintains such transmembrane associations in skeletal muscle (10,66). It binds to laminin in the basal lamina that surrounds muscle fibers. Within muscle fibers, the integrin associates with the subsarcolemmal cytoskeleton network through focal adhesion complexes (5). The ␣ 7 ␤ 1 -integrin is distributed along the sarcolemma at costameres, and it is also concentrated at neuromuscular and myotendinous junctions (2,48). This localization suggests that the integrin has a pivotal role in maintaining these specialized structures and their functions in skeletal muscle. Congenital myopathies caused by mutations in t...

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“…Qu-Petersen et al demonstrated restoration of dystrophin production in mdx mice (a mouse model of DMD which has a point mutation within its dystrophin gene) after transplantation of allogenic MDSCs [37]. Similar results were obtained by injecting satellite cells, mesoangioblasts and pericytes in high densities in to dystrophic muscle [52,66,67]. More recently, attention is focused on the use of genetically modified MDSCs, e.g.…”

Section: Regeneration Of Skeletal Musclementioning

confidence: 87%

Adult stem cells derived from skeletal muscle — biology and potential

2013

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Skeletal muscle contains at least two distinct populations of adult stem cells — satellite cells and multipotent muscle-derived stem cells. Monopotential satellite cells are located under the basal lamina of muscle fibers. They are capable of giving rise only to cells of myogenic lineage, which play an important role in the processes of muscle regeneration. Multipotent muscle-derived stem cells are considered to be predecessors of the satellite cells. Under proper conditions, both in vitro and in vivo, they undergo myogenic, cardiogenic, chondrogenic, osteogenic and adipogenic differentiation. The main purpose of the present article is to summarize current information about adult stem cells derived from skeletal muscle, and to discuss their isolation and in vitro expansion techniques, biological properties, as well as their potential for regenerative medicine.

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Multipotential Mesoangioblast Stem Cell Therapy in the Mdx/Utrn ^-/- mouse model for Duchenne muscular dystrophy

Abstract: Mesoangioblasts differentiate into multiple cell types damaged during the progression of severe muscle disease and protect fibers from damage. As such, they are good candidates for therapy of Duchenne muscular dystrophy and perhaps other neuromuscular diseases.

Cited by 65 publications

References 60 publications

Systemic Delivery of Allogenic Muscle Stem Cells Induces Long-Term Muscle Repair and Clinical Efficacy in Duchenne Muscular Dystrophy Dogs

Systemic Delivery of Allogenic Muscle Stem Cells Induces Long-Term Muscle Repair and Clinical Efficacy in Duchenne Muscular Dystrophy Dogs

Increasing α₇β₁-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression

Adult stem cells derived from skeletal muscle — biology and potential

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Multipotential Mesoangioblast Stem Cell Therapy in the Mdx/Utrn -/- mouse model for Duchenne muscular dystrophy

Abstract: Mesoangioblasts differentiate into multiple cell types damaged during the progression of severe muscle disease and protect fibers from damage. As such, they are good candidates for therapy of Duchenne muscular dystrophy and perhaps other neuromuscular diseases.

Cited by 65 publications

References 60 publications

Systemic Delivery of Allogenic Muscle Stem Cells Induces Long-Term Muscle Repair and Clinical Efficacy in Duchenne Muscular Dystrophy Dogs

Systemic Delivery of Allogenic Muscle Stem Cells Induces Long-Term Muscle Repair and Clinical Efficacy in Duchenne Muscular Dystrophy Dogs

Increasing α7β1-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression

Adult stem cells derived from skeletal muscle — biology and potential

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Product

Resources

About

Multipotential Mesoangioblast Stem Cell Therapy in the Mdx/Utrn ^-/- mouse model for Duchenne muscular dystrophy

Increasing α₇β₁-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression