MMP1 gene expression enhances myoblast migration and engraftment following implanting into mdx/SCID mice

Myoblast transplantation (MT) is a method to introduce healthy genes into abnormal skeletal muscle. It has been considered as a therapeutic modality in the last few decades for diseases such as Duchenne Muscular Dystrophy (DMD). However, challenges including cell death and poor graft engraftment have limited its application. The current experiment utilizes MMP1 gene transfer to improve the efficacy of myoblast transplantation into the diseased dystrophic skeletal muscle of mdx mice. Our results indicated that MMP1 expression can promote myogenic differentiation and fusion capacities, increase migration of MMP1 expressing myoblasts in vitro, as well as improve engraftment of dystrophin positive myofibers in vivo. Taken together, our observation suggests that the addition of MMP1 can overcome limitations in MT and improve its clinical efficacy.

[1]  Yohan Choi,et al.  Regeneration of Soft Tissues Is Promoted by MMP1 Treatment after Digit Amputation in Mice , 2013, PloS one.

[2]  Giulio Cossu,et al.  Corrigendum: Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs , 2013, Nature.

[3]  M. Ciemerych,et al.  Decrease of MMP-9 activity improves soleus muscle regeneration. , 2012, Tissue engineering. Part A.

[4]  M. Urso,et al.  Growth Factors , Cytokines , Cell Cycle Molecules Relaxin Regulates MMP Expression and Promotes Satellite Cell Mobilization During Muscle Healing in Both Young and Aged Mice , 2010 .

[5]  M. Fiszman,et al.  MMP‐9 overexpression improves myogenic cell migration and engraftment , 2010, Muscle & nerve.

[6]  J. Huard,et al.  Isolating stem cells from soft musculoskeletal tissues. , 2010, Journal of visualized experiments : JoVE.

[7]  F. Ambrosio,et al.  Effect of VEGF on the regenerative capacity of muscle stem cells in dystrophic skeletal muscle. , 2009, Molecular therapy : the journal of the American Society of Gene Therapy.

[8]  Yong Li,et al.  Biochemical insights into the role of matrix metalloproteinases in regeneration: challenges and recent developments. , 2009, Future medicinal chemistry.

[9]  B. Jefferson,et al.  Matrix metalloproteinase-1 promotes muscle cell migration and differentiation. , 2009, The American journal of pathology.

[10]  R. Koepsel,et al.  Matrix metalloproteinase-1 treatment of muscle fibrosis. , 2008, Acta biomaterialia.

[11]  L. Morandi,et al.  Altered extracellular matrix transcript expression and protein modulation in primary Duchenne muscular dystrophy myotubes. , 2007, Matrix biology : journal of the International Society for Matrix Biology.

[12]  Juan Li,et al.  Decorin gene transfer promotes muscle cell differentiation and muscle regeneration. , 2007, Molecular therapy : the journal of the American Society of Gene Therapy.

[13]  J. Chamberlain,et al.  Systemic administration of micro-dystrophin restores cardiac geometry and prevents dobutamine-induced cardiac pump failure. , 2007, Molecular therapy : the journal of the American Society of Gene Therapy.

[14]  J. Kaar,et al.  Matrix metalloproteinase-1 therapy improves muscle healing. , 2007, Journal of applied physiology.

[15]  E. E. El Fahime,et al.  A new pro-migratory activity on human myogenic precursor cells for a synthetic peptide within the E domain of the mechano growth factor. , 2007, Experimental cell research.

[16]  P. Nido,et al.  Muscle engraftment of myogenic progenitor cells following intraarterial transplantation , 2006, Muscle & nerve.

[17]  J. Bouchard,et al.  Dystrophin Expression in Muscles of Duchenne Muscular Dystrophy Patients After High-Density Injections of Normal Myogenic Cells , 2006, Journal of neuropathology and experimental neurology.

[18]  D. Skuk.  Myoblast transplantation for inherited myopathies: a clinical approach , 2004, Expert opinion on biological therapy.

[19]  P. Mills,et al.  GROWTH FACTORS IMPROVE THE IN VIVO MIGRATION OF HUMAN SKELETAL MYOBLASTS BY MODULATING THEIR ENDOGENOUS PROTEOLYTIC ACTIVITY , 2004, Transplantation.

[20]  Yong Li,et al.  Transforming growth factor-beta1 induces the differentiation of myogenic cells into fibrotic cells in injured skeletal muscle: a key event in muscle fibrogenesis. , 2004, The American journal of pathology.

[21]  J. Bouchard,et al.  Dystrophin expression in myofibers of Duchenne muscular dystrophy patients following intramuscular injections of normal myogenic cells. , 2004, Molecular therapy : the journal of the American Society of Gene Therapy.

[22]  E. Carmeli,et al.  Matrix metalloproteinases and skeletal muscle: A brief review , 2004, Muscle & nerve.

[23]  T. Takala,et al.  Synthesis and degradation of type IV collagen in rat skeletal muscle during immobilization in shortened and lengthened positions. , 2003, Acta physiologica Scandinavica.

[24]  T. Partridge.  Stem cell route to neuromuscular therapies , 2003, Muscle & nerve.

[25]  Yong Li,et al.  Differentiation of muscle-derived cells into myofibroblasts in injured skeletal muscle. , 2002, The American journal of pathology.

[26]  Yong Li,et al.  Muscle injuries and repair: current trends in research. , 2002, The Journal of bone and joint surgery. American volume.

[27]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[28]  N. Caron,et al.  In vivo migration of transplanted myoblasts requires matrix metalloproteinase activity. , 2000, Experimental cell research.

[29]  T. Best,et al.  Muscle injury and repair. , 2000, Physical medicine and rehabilitation clinics of North America.

[30]  R. Mulligan,et al.  Dystrophin expression in the mdx mouse restored by stem cell transplantation , 1999, Nature.

[31]  J. Tremblay,et al.  Increased Myogenic Potential and Fusion of Matrilysin-Expressing Myoblasts Transplanted in Mice , 1999, Cell transplantation.

[32]  R. Mantegazza,et al.  Transforming growth factor-beta1 and fibrosis in congenital muscular dystrophies. , 1999, Neuromuscular disorders : NMD.

[33]  L. Kunkel,et al.  The fate of individual myoblasts after transplantation into muscles of DMD patients , 1997, Nature Medicine.

[34]  M. Grounds,et al.  Rapid death of injected myoblasts in myoblast transfer therapy , 1996, Muscle & nerve.

[35]  R. R. Rice,et al.  Myoblast transfer in the treatment of Duchenne's muscular dystrophy. , 1995, The New England journal of medicine.

[36]  C. Richards,et al.  Results of a Triple Blind Clinical Study of Myoblast Transplantations without Immunosuppressive Treatment in Young Boys with Duchenne Muscular Dystrophy , 1993, Cell transplantation.

[37]  H. Blau,et al.  Anorectal incontinence in myotonic dystrophy: a myopathic involvement of pelvic floor muscles. , 1992 .

[38]  K. Davies,et al.  Human dystrophin expression in mdx mice after intramuscular injection of DNA constructs , 1991, Nature.

[39]  T. Partridge.  Invited review: Myoblast transfer: A possible therapy for inherited myopathies? , 1991, Muscle & nerve.

[40]  L. Kunkel,et al.  Conversion of mdx myofibres from dystrophin-negative to -positive by injection of normal myoblasts , 1989, Nature.

[41]  D. Watt,et al.  Incorporation of donor muscle precursor cells into an area of muscle regeneration in the host mouse , 1982, Journal of the Neurological Sciences.

[42]  H. Moriyama,et al.  Regulation of connective tissue remodeling in the early phase of denervation in a rat skeletal muscle. , 2013, Biomedical research.

[43]  Yong Li,et al.  Matrix metalloproteinase inhibition negatively affects muscle stem cell behavior. , 2013, International journal of clinical and experimental pathology.

[44]  B. Picard,et al.  Age-related changes and location of type I, III and IV collagens during skeletal muscle development of double-muscled and normal bovine foetuses , 2004, Journal of Muscle Research & Cell Motility.

[45]  S. Bhattacharya,et al.  Heterogeneity of dystrophin expression in patients with Duchenne and Becker muscular dystrophy , 2004, Acta Neuropathologica.

[46]  G. Fields,et al.  Matrix metalloproteinases and collagen catabolism. , 2002, Biopolymers.

[47]  R. Worton,et al.  Myoblast transfer in DMD: problems in the interpretation of efficiency. , 1992, Muscle & nerve.

[48]  Eric P. Hoffman,et al.  Dystrophin: The protein product of the duchenne muscular dystrophy locus , 1987, Cell.

[49]  A. Bailey,et al.  Skeletal muscle injury—molecular changes in the collagen during healing , 1985, Research in experimental medicine. Zeitschrift fur die gesamte experimentelle Medizin einschliesslich experimenteller Chirurgie.