Genes & CellsGenes & CellsГены и КлеткиGenes and Cells2313-18292500-2562Human Stem Cells Institute21771510.23868/gc217715ReviewsНаучные обзорыReview ArticleProspects for the use of gene and cell therapy for the treatment of muscular dystrophyПерспективы использования генной и клеточной терапий для лечения мышечных дистрофийSukachA. N.СукачА. Н.
Ukraine

department of cryobiochemistry

отдел криобиохимии

redaktor@celltranspl.ruInstitute of Cryobiology and Cryomedicine of the National Academy of Sciences of UkraineИнститут проблем криобиологии и криомедицины НАН Украины150220061244501102202311022023Copyright ©; 2006, Eco-VectorCopyright ©; 2006, Эко-Вектор2006Eco-VectorЭко-Векторhttps://genescells.ru/2313-1829/article/view/217715

The review discusses modern approaches to the treatment of muscular dystrophy, a heterogeneous group of neuromuscular diseases that manifest themselves as progressive muscle weakness, as well as their partial loss, which in many cases leads to death. There are currently no effective medical methods for the treatment of dystrophies. However, there are several investigated therapeutic options for the treatment of muscular dystrophy, including gene therapy and transplantation of myogenic progenitor cells - cell therapy. The article discusses the achievements and difficulties on the way of introducing gene therapy into the clinical practice of treatment of muscular dystrophy. Special attention is paid to cell therapy, a promising direction of regenerative medicine, which gives hope for the cure of many previously incurable hereditary and acquired diseases. Potential sources of human somatic and embryonic stem/progenitor cells that can be used both as objects of application of genetic engineering methods and for cell therapy of muscular dystrophy are discussed. The problems that stand in the way of the successful introduction into clinical practice of the treatment of muscular dystrophy of human stem/progenitor cells are discussed.

В обзоре обсуждаются современные подходы к лечению мышечных дистрофий - гетерогенной группы нервно-мышечных заболеваний, которые проявляются в виде прогрессирующей слабости мышц, а также их частичной потери, что во многих случаях приводит к смерти. Эффективных медикаментозных способов лечения дистрофий в настоящее время нет. Однако существует несколько исследуемых терапевтических вариантов лечения мышечных дистрофий, включающих генную терапию и трансплантацию миогенных клеток-предшественников - клеточную терапию. В статье обсуждаются достижения и трудности на пути внедрения генной терапии в клиническую практику лечения мышечных дистрофий. Особое внимание уделено клеточной терапии, перспективному направлению регенеративной медицины, дающему надежду на излечение многих ранее не излечимых как наследственных, так и приобретенных заболеваний. Обсуждаются потенциальные источники соматических и эмбриональных стволовых/прогениторных клеток человека, которые могут использоваться как в качестве объектов приложения генно-инженерных методов, так и для клеточной терапии мышечных дистрофий. Обсуждаются проблемы, стоящие на пути успешного внедрения в клиническую практику лечения мышечных дистрофий стволовых/прогениторных клеток человека.

myodystrophystem cellsgene therapycell therapyмиодистрофиястволовые клеткигенотерапияклеточная терапияO’Brien K.F., Kunkel L.M. Dystrophin and muscular dystrophy: past, present, and future. Mol. Genet. Metab. 2001 ; 74: 75-88.Durbeej M., Campbell K.P. Muscular dystrophies involving the dystrophinglycoprotein complex: an overview of current mouse models. Curr. Opin. Genet. Dev. 2002; 12: 349-61.Ehmsen J., Poon E., Davies K. The dystrophin-associated protein complex. J. Cell Sci. 2002; 115: 2801 - 3.Coffey A.J., Roberts R.G., Green E.D. et al. Construction of a 2.6-Mb contig in yeast artificial chromosomes spanning the human dystrophin gene using an STS-based approach. Genomics 1992; 12: 474-84.Monaco A.P., Walker A.P., Millwood I. et al. A yeast artificial chromosome contig containing the complete Duchenne muscular dystrophy gene. Genomics 1992; 12: 465-73.Roberts R.G., Coffey A.J., Bobrow M, Bentley D.R. Exon structure of the human dystrophin gene. Genomics 1993; 16: 536-8.Partridge T.A. Models of dystrophinopathy, pathological mechanisms and assessment of therapies in Dystrophin, Gene , Protein and Cell Biology [Brown S.C., Lucy J.A. eds.), Cambridge, U.K. ; New York: Cambridge University Press; 1997; 310-31.Wilton S.D., Lloyd F., Carville K. et al. Specific removal of the nonsense mutation from the mdx dystrophin mRNA using antisense oligonucleotides. Neuromuscul. Disord. 1999; 9 [5): 330-8Fassati A., Murphy S., Dickson, G. Gene therapy of Duchenne muscular dystrophy. Adv. Genet. 1997; 35: 117-53.Howell J.M., Lochmuller H., O’Hara A. et al. High-level dystrophin expression after adenovirus-mediated dystrophin minigene transfer to skeletal muscle of dystrophic dogs: prolongation of expression with immunosuppression. Human Gene Ther. 1998; 9: 629.Wang B., Li J., Xiao X. Adeno-associated virus vector carrying human minidystrophin genes effectively ameliorates muscular dystrophy in mdx mouse model. Proc. Natl. Acad. Sci. USA 2000; 97: 13714- 9.Harper S.Q., Hauser M.A., Dellorusso C. et al. Modular flexibility of dystrophin: implications for gene therapy of Duchenne muscular dystrophy. Nat. Med. 2002; 8: 253-61.Зеленин А.В. , Кайгородов В.А., Прасолов В.С. Генная терапия сегодня и завтра. Мол. биол. 1998; 32: 219-28.Баранов В.С. Генная терапия - медицина 21 века. Соросовский Образовательный Журнал 1999; 3: 63-8.Love D.R., Hill D.F., Dickson G. et al. An autosomal transcript in skeletal muscle with homology to dystrophin. Nature 1989; 339: 55-8.1 6. Clerk A., Morris G.E., Dubowitz V. et al. Dystrophin-related protein, utrophin, in normal and dystrophic human fetal skeletal muscle. Histochem. J. 1993; 25: 554-61.Tinsley J.M., Davies K.E. Utrophin: a potential replacement for dystrophin? Neuromuscular Disorders 1993; 3: 537-9.Tinsley J.M., Potter A.C., Phelps S.R. et al. Amelioration of the dystrophic phenotype of mdx mice using a truncated utrophin transgene. Nature 1996; 384: 349-53.Rafael J.A., Tinsley J.M., Potter A.C. et al. Skeletal muscle-specific expression of a utrophin transgene rescues utrophin-dystrophin deficient mice. Nat. Genet. 1998; 19: 79-82.Gilbert R., Nalbanoglu J., Tinsley J.M. et al. Efficient utrophin expression following adenovirus gene transfer in dystrophic muscle. Biochem. Biophys. Res. Commun. 1998; 242: 244-7.Friedenstein A., Owen M. Stromal stem cells: marrow derived osteogenic progenitors. CIBA Found. Symp. 1988; 136: 42-60.Anderson D.J., Gage F.H., Weissman I.L. Can stem cells cross lineage boundaries? Nat. Med. 2001 ; 7: 393-5.Blau H.M., Brazelton T.R., Weimann J.M. The evolving concept of a stem cell: entity or function? Cell 2001 ; 105: 829-41.Krause D.S., Theise N.D., Collector M.I. et al. Multi-organ, multi-lineage engraftment by a single BMderived stem cell. Cell 2001 ; 105: 369-77.Bjornson C.R., Rietze R.L., Reynolds B.A. et al. Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. Science 1999; 283: 534-7.Clarke D.L., Johansson C.B., Wilbertz J. et al. Generalized potential of adult neural stem cells. Science 2000; 288: 1660-3.Rietze R.L., Valcanis H., Brooker G.F. et al. Purification of a pluripotent neural stem cell from the adult mouse brain. Nature 2001; 412: 736-39.Alonso L., Fuchs E. Stem cells of the skin epithelium. Proc. Natl. Acad. Sci. USA 2003; 100 (Suppl. 1): 11830-5.Beltrami A.P., Barlucchi L., Torella D. et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 2003; 114: 763-76.Gussoni E., Soneoka Y., Strickland C. et al.: Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 1999; 401: 390-4.Jackson K.A., Mi T., Goodell M.A. Hematopoietic potential of stem cells isolated from murine skeletal muscle. Proc. Natl. Acad. Sci. USA 1999; 96: 14482-6.Heslop L., Morgan J.E., Partridge T.A. Evidence for a myogenic stem cell that is exhausted in dystrophic muscle. J. Cell Sci. 2000; 113(Pt 12): 2299-308.Asakura A., Seale P., Girgis-Gabardo A., Rudnicki M.A. Myogenic specification of side population cells in skeletal muscle. J. Cell Biol. 2002; 159: 123-34.Cao B., Zheng B., Jankowski R.J. et al. Muscle stem cells differentiate into haematopoietic lineages but retain myogenic potential. Nat. Cell Biol. 2003; 5(7): 640-6.Wakitani S., Saito T., Caplan A.I. Myogenic cells derived from rat BM mesenchymal stem cells exposed to 5-azacytidine. Muscle Nerve 1995; 18: 1417-26.Jiang Y., Jahagirdar B.N., Reinhardt R.L. et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002; 418: 41-49.Brazelton T.R., Rossi F.M., Keshet G.I., Blau H.M. From marrow to brain: expression of neuronal phenotypes in adult mice. Science 2000; 290: 1775-9.Mezey E., Chandross K.J., Harta G. et al. Turning blood into brain: cells bearing neuronal antigens generated in vivo from BM. Science 2000; 290: 1779-82.Lagasse E., Connors H., Al-Dhalimy M. et al. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat. Med. 2000; 6: 1229-34.Ferrari G., Cusella-De Angelis G., Coletta M. et al. Muscle regeneration by bone marrow-derived myogenic progenitors. Science 1998; 279: 1528-30.Bittner R.E., Schofer C., Weipoltshammer K. et al. Recruitment of bonemarrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice. Anat. Embryol. (Berl) 1999; 199: 391 -6.Ferrari G., Stornaiuolo A., Mavilio F. Failure to correct murine muscular dystrophy. Nature 2001; 411: 1014-5.Gussoni E., Bennett R.R., Muskiewicz K.R. et al. Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation. J. Clin. Invest. 2002; 110: 807-14.Romanov Y.A., Svintsitskaya V.A., Smirnov V.N. Searching for Alternative Sources of Postnatal Human Mesenchymal Stem Cells: Candidate MSC-Like Cells from Umbilical Cord. Stem Cells 2003; 21: 105-10.Kong K.Y., Ren J., Kraus M. et al. Human Umbilical Cord Blood Cells Differentiate into Muscle in sjl Muscular Dystrophy Mice. Stem Cells 2004; 22: 981 -3.Bischoff R. The satellite cell and muscle regeneration. In: Myology, 2nd Edition, Engel AG, Franzini-Armstrong C (Eds), McGraw Hill 1994; 1: 97-119.Seale P., Rudnicki M.A. A new look at the origin, function, and ‘stem-cell’ status of muscle satellite cells. Dev. Biol. 2000; 218: 115-24.Grounds M.D., McGeachie J.K. A model of myogenesis in vivo, derived from detailed autoradiographic studies of regenerating skeletal muscle, challenges the concept of quantal mitosis. Cell Tissue Res. 1987; 250: 563-9.Rantanen J., Hurme T., Lukka R. et al. Satellite cell proliferation and the expression of myogenin and desmin in regenerating skeletal muscle: evidence for two different populations of satellite cells. Lab. Invest. 1995; 72: 341 -7.Schultz E. Satellite cell proliferative compartments in growing skeletal muscles. Dev. Biol. 1996; 175: 84-94.De Angelis L., Berghella L., Coletta M. et al.: Skeletal myogenic progenitors originating from embryonic dorsal aorta coexpress endothelial and myogenic markers and contribute to postnatal muscle growth and regeneration. J. Cell Biol. 1999; 147: 869-78.Beauchamp J.R., Heslop L., Yu D.S. et al. Expression of CD34 and Myf5 defines the majority of quiescent adult skeletal muscle satellite cells. J. Cell Biol. 2000; 151: 1221-34.Wada M.R., Inagawa-Ogashiwa M., Shimizu S. et al. Generation of different fates from multipotent muscle stem cells. Development 2002; 129: 2987-95.Charge. S.B., Rudnicki M.A. Cellular and Molecular Regulationof Muscle Regeneration. Physiol. Rev. 2004; 84: 209-38.Karpati G., Pouliot Y., Zubrzycka-Gaarn E. et al. Dystrophin is expressed in mdx skeletal muscle fibers after normal myoblast implantation. Am J. Pathol. 1989; 135: 27-32.Partridge T.A., Morgan J.E., Coulton G.R. et al. Conversion of mdx myofibers from dystrophin negative to positive by injection of normal myoblasts. Nature 1989; 337: 176-9.Gussoni E., Pavlath G.K., Lanctot A.M., et al. Normal dystrophin transcripts detected in Duchenne muscular dystrophy patients after myoblast transplantation. Nature 1992; 356: 435-8.Karpati G., Ajdukovic D., Arnold D. et al. Myoblast transfer in Duchenne muscular dystrophy. Ann. Neurol. 1993; 34: 8-17.Mendell J.R., Kissel J.T., Amato A.A. et al. Myoblast transfer in the treatment of Duchenne’s muscular dystrophy. N. Engl. J. Med. 1995; 333: 832-8.Morandi L., Bernasconi P., Gebbia M. et al. Lack of mRNA and dystrophin expression in DMD patients three months after myoblast transfer. Neuromuscul. Disord. 1995; 5: 291-5.Neumeyer A.M., Cros D., McKenna-Yasek D. et al. Pilot study of myoblast transfer in the treatment of Becker muscular dystrophy. Neurology 1998; 51: 589-92.Partridge T., Lu Q.L., Morris G., Hoffman E. Is myoblast transplantation effective?, Nature Med. 1998; 4: 1208.Beauchamp J.R., Morgan J.E., Pagel C.N., Partridge T.A. Dynamics of myoblast transplantation reveal a discrete minority of precursors with stem celllike properties as the myogenic source. J. Cell Biol. 1999; 144: 1113-22.Roy R., Tremblay J.P., Huard J. et al. Antibody formation after myoblast transplantation in Duchenne-dystrophic patients, donor HLA compatible. Transpl. Proc. 1993; 25: 995-7.Urish K., Kanda Y., Huard J. Initial failure in myoblast transplantation therapy has led the way toward the isolation of muscle stem cells: potential for tissue regeneration. Curr. Top. Dev. Biol. 2005; 68: 263-80.Camirand G., Rousseau J., Ducharme M.E. et al. Dystrophin expression in myofibers of Duchenne muscular dystrophy patients following intramuscular injections of normal myogenic cells. Molecular Therapy 2004; 9(3): 475-82.Zhao P., Hoffman E. P. Embryonic myogenesis pathways in muscle regeneration. Dev. Dyn. 2004; 229(2): 380-92.Qu Z., Balkir L., van Deutekom J.C., Robinson P.D., Pruchnic R., Huard J. Development of approaches to improve cell survival in myoblast transfer therapy. J. Cell Biol. 1998; 142: 1257-67.Lee J.Y., Qu-Petersen Z., Cao B. et al. Clonal isolation of muscle-derived cells capable of enhancing muscle regeneration and bone healing. J. Cell Biol. 2000; 150: 1085-1100.Qu-Petersen Z., Deasy B., Jankowski R. et al. Identification of a novel population of muscle stem cells in mice: potential for muscle regeneration. J. Cell Biol. 2002; 157: 851-64.Torrente Y., Tremblay J.P., Pisati F. et al. Intra-arterial injection of muscle- derived CD34(+)Sca-1(+) stem cells restores dystrophin in mdx mice. J. Cell Biol. 2001; 152: 335-48.Zhou S., Schuetz J.D., Bunting K.D. et al. The ABC transporter Bcrp1/ ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med. 2001 ; 7: 1028-34.Zhou S., Morris J.J., Barnes Y., et al. Bcrp1 gene expression is required for normal numbers of side population stem cells in mice, and confers relative protection to mitoxantrone in hematopoietic cells in vivo. Proc. Natl. Acad. Sci. USA 2002; 99: 12339-44.Seale P., Sabourin L.A., Girgis-Gabardo A. et al. Pax7 is required for the specification of myogenic satellite cells. Cell 2000; 102: 777-86.Castro R.F., Jackson K.A., Goodell M.A. et al. Failure of BM cells to transdifferentiate into neural cells in vivo. Science 2002; 297 (Issue 5585): 1299.Wagers A.J., Sherwood R.I., Christnsen J.L., Weissman I.L. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 2002; 5: 5.Schulze M., Belema-Bedada F., Technau A., Braun T. Mesenchymal stem cells are recruited to striated muscle by NFAT/IL-4-mediated cell fusion. Genes Dev. 2005; 19(15): 1787-98.Liang Y., Van Zant G., Szilvassy S.J. Effects of aging on the homing and engraftment of murine hematopoietic stem and progenitor cells. Blood 2005; 106: 1479-87.Amit M., Carpenter M.K., Inokuma M.S. et al. Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of culture. Dev. Biol. 2000; 227: 271-8.Thomson J.A., Itskovitz-Eldor J., Shapiro S.S. et al. Embryonic stem cell lines derived from human blastocyst. Science 1998; 282: 1145-7.Reubinoff B.E., Pera M.F., Fong C.Y. et al. Embryonic stem cell lines from human blastocysts: Somatic differentiation in vitro. Nature. Biotechnology 2000; 18: 399-404.Hochedlinger K., Jaenisch R. Nuclear transplantation, embryonic stem cells, and the potential for cell therapy. N. Engl. J. Med. 2003; 349: 275-86.Jaenisch R Human cloning - the science and ethics of nuclear transplantation. N. Engl. J. Med. 2004; 351: 2787-91.Minasi M.G., Riminucci M., De Angelis L. et al. The mesoangioblast: a multipotent, self-renewing cell that originates from the dorsal aorta and differentiates into most mesodermal tissues. Development 2002; 129: 2773-83.Sampaoles M., Torrente Y, Innocenzi A. et al. Cell therapy of alphasarcoglycan null dystrophic mice through intra-arterial delivery of mesoangioblasts. Science 2003; 301: 487-92.Palumbo R., Sampaolesi M., De Marchis F. et al. Extracellular HMGB1, a signal of tissue damage, induces mesoangioblast migration and proliferation. JCB 2004; 164 (3): 441-49.Cossu G., Bianco P. Mesoangioblasts-vascular progenitors for extravascular mesodermal tissues. Curr. Opin. Genet. Dev. 2003; 13: 537-42