Gene transfer into skeletal muscles by isogenic myoblasts.

The best way to overcome immunorejection in heterologous myoblast transfer (HMT) is by the use of immunodeficient and/or highly immunosuppressed mice as hosts. The same may be attained by autologous myoblast transfer (AMT). In this paper, we describe myoblast transfer in mdx and normal mice where the donor myogenic cells originated from highly inbred litter mates that are considered to be isogenic and thus the procedure is analogous to AMT. The myoblasts were marked in vitro with Rous Sarcoma Virus (RSV)-luciferase (Lux) or RSV-beta-galactosidase (LacZ) reporter genes through transduction mediated by an autonomously replication-defective recombinant human adenovirus. This permitted us to follow their fate after transplantation. mdx and normal mice were irradiated with 20 Gray gamma rays; necrosis and regeneration were induced by intramuscular notexin prior to myoblast injection. In both mdx and normal mice, the expression of luciferase rapidly declined after the injection implying that a large portion of the injected myoblasts were lost by 48 hr, due to undetermined cause(s). The surviving, injected myoblasts well-mosaicized large groups of host fibers but only in the immediate vicinity of the injection. Substantial expression of the reporter gene continued up to 1 month post-transplantation in normal mice, but there was a gradual decline and eventual disappearance of the reporter gene expression in mdx mice. This latter phenomenon was due to the ongoing intense necrosis of muscle fibers in mdx. There was no evidence of immunorejection. These experiments indicate that even in the absence of immunorejection, myoblast transfer suffers from important negative features: major loss of myoblasts within 48 hr after the injection and lack of significant spread of the injected cells from the injection site in the host muscle. These factors, plus the limited proliferative and fusion capacity of Duchenne muscular dystrophy (DMD) myoblasts, make them less than an ideal vector for the dystrophin cDNA for dystrophin gene replacement therapy in DMD.

[1]  Hanns Lochmüller,et al.  Cultured human myoblasts and myotubes show markedly different transducibility by replication-defective adenovirus recombinants. , 1994, Gene therapy.

[2]  G. Acsadi,et al.  A differential efficiency of adenovirus-mediated in vivo gene transfer into skeletal muscle cells of different maturity. , 1994, Human molecular genetics.

[3]  J. Huard,et al.  Human myoblast transplantation in immunodeficient and immunosuppressed mice: Evidence of rejection , 1994, Muscle & nerve.

[4]  J. Tremblay,et al.  High efficiency of muscle regeneration after human myoblast clone transplantation in SCID mice. , 1994, The Journal of clinical investigation.

[5]  P. Tonali,et al.  Retroviral vector-mediated gene transfer into human primary myogenic cells leads to expression in muscle fibers in vivo. , 1993, Human gene therapy.

[6]  E. Schultz,et al.  Dystrophin expression improves myofiber survival in mdx muscle following intramuscular plasmid DNA injection. , 1993, Human molecular genetics.

[7]  G. Acsadi,et al.  Invited Review. The potential for gene therapy in duchenne muscular dystrophy and other genetic muscle diseases , 1993, Muscle & nerve.

[8]  M. Perricaudet,et al.  Long–term correction of mouse dystrophic degeneration by adenovirus–mediated transfer of a minidystrophin gene , 1993, Nature genetics.

[9]  George Karpati,et al.  Myoblast transfer in duchenne muscular dystrophy , 1993, Annals of neurology.

[10]  Jon A. Wolff,et al.  Long-term correction of rat model of Parkinson's disease by gene therapy , 1993, Nature.

[11]  J. Huard,et al.  Utilization of an Antibody Specific for Human Dystrophin to Follow Myoblast Transplantation in Nude Mice , 1993, Cell transplantation.

[12]  P. Briand,et al.  Efficient adenovirus-mediated transfer of a human minidystrophin gene to skeletal muscle of mdx mice , 1993, Nature.

[13]  G. Acsadi,et al.  Long-term persistence of plasmid DNA and foreign gene expression in mouse muscle. , 1992, Human molecular genetics.

[14]  H. Sarnat.  Vimentin and desmin in maturing skeletal muscle and developmental myopathies , 1992, Neurology.

[15]  J. Bouchard,et al.  Human myoblast transplantation: Preliminary results of 4 cases , 1992, Muscle & nerve.

[16]  K. Kurachi,et al.  Expression of human factor IX in mice after injection of genetically modified myoblasts. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[17]  H. Blau,et al.  Normal dystrophin transcripts detected in Duchenne muscular dystrophy patients after myoblast transplantation , 1992, Nature.

[18]  J. Mandel,et al.  Adenovirus as an expression vector in muscle cells in vivo. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[19]  K. Davies,et al.  Retroviral‐mediated transfer of a dystrophin minigene into mdx mouse myoblasts in vitro , 1992, FEBS letters.

[20]  H. Blau,et al.  Systemic delivery of human growth hormone by injection of genetically engineered myoblasts. , 1991, Science.

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

[22]  J. Huard,et al.  Dystrophin expression in myotubes formed by the fusion of normal and dystrophic myoblasts , 1991, Muscle & nerve.

[23]  B. Massie,et al.  High level expression in 293 cells of the herpes simplex virus type 2 ribonucleotide reductase subunit 2 using an adenovirus vector. , 1990, The Journal of general virology.

[24]  Y. Pouliot,et al.  Dystrophin is expressed in mdx skeletal muscle fibers after normal myoblast implantation. , 1989, The American journal of pathology.

[25]  E A Barnard,et al.  The molecular basis of muscular dystrophy in the mdx mouse: a point mutation. , 1989, Science.

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

[27]  D. Watt,et al.  Partial correction of an inherited biochemical defect of skeletal muscle by grafts of normal muscle precursor cells , 1988, Journal of the Neurological Sciences.

[28]  K. Berkner.  Development of adenovirus vectors for the expression of heterologous genes. , 1988, BioTechniques.

[29]  Hideo Sugita,et al.  Immunostaining of skeletal and cardiac muscle surface membrane with antibody against Duchenne muscular dystrophy peptide , 1988, Nature.

[30]  R. Hodges,et al.  The Duchenne muscular dystrophy gene product is localized in sarcolemma of human skeletal muscle , 1988, Nature.

[31]  S. Leahy.  Eight ‘Musts’ for Biotechnology , 1988, Bio/Technology.

[32]  D. Hanahan,et al.  Infection of eucaryotic cells by helper-independent recombinant adenoviruses: early region 1 is not obligatory for integration of viral DNA , 1984, Journal of virology.

[33]  K. Moore,et al.  X chromosome-linked muscular dystrophy (mdx) in the mouse. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[34]  H. Blau,et al.  Defective myoblasts identified in Duchenne muscular dystrophy. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[35]  T. Tsukahara,et al.  Negative immunostaining of Duchenne muscular dystrophy(DMD) and mdx muscle surface membrane with antibody against synthetic peptide fragment predicted from DMD cDNA. , 1988 .

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