Nonmyeloablative bone marrow cells transplantation restores dystrophin synthesis in the muscles of MDX mice


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Duchenne muscular dystrophy is an X-linked recessive muscular dystrophy associated with a mutations in the dystrophin protein gene. The most common laboratory model of Duchenne muscular dystrophy is mdx mice. The striated muscle fibers of mdx mice are characterized by the absence of dystrophin, the presence of centrally located nuclei, and the high level of renewal of the striated muscle fibers. In addition, mdx mice show a morphological aberrations at neuromuscular junctions, expressed in the breakdown of large clusters of acetylcholine receptors in the form of branches into small clusters in the form of islets. One approach to treating muscular dystrophy in mdx mice may be the nonmyeloablative transplantation of wild-type bone marrow cells after X-ray irradiation of mdx mice at a dose of 3 Gy. The aim of this work is to evaluate the effect of nonmyeloabla-tive transplantation of wild-type bone marrow cells on dystrophin synthesis and the structure of neuromuscular junctions of mdx mice. Mdx mice were irradiated with X-rays at a dose of 3 Gy, after 24 hours was performed intravenous transplantation of bone marrow cells of C57BL/6 mice. The m. quariceps femoris and diaphragm were examined 2, 4, 6, 9, 12 months after transplantation. Muscle studies were performed using immunohisto-chemical methods of study (immunohistochemical staining with antibodies to dystrophin). The neuromuscular junctions were stained with tetramethylrodamine-a-bungarotoxin. After intravenous bone marrow cells transplantation, the part of dystrophin-positive muscle fibers in the muscle quadriceps femoris was shown to increase to a 27,6±6,7% 6 months after transplantation. After 12 months, the part of dystrophin-positive muscle fibers decreased to 5,1±1,1%. There was also an increase in the proportion of striated muscle fibers without centrally located nuclei and a decrease in the part of dead striated muscle fibers. Similar changes were found in the striated muscle fibers of the diaphragm of mdx mice. In addition, transplantation of bone marrow cells after irradiation at a dose of 3 Gy increases the part of neuromuscular junctions with normal structure. Thus, nonmy-eloablative transplantation of wild-type bone marrow cells can be considered as one way to treat monogenic disease of striated muscle fibers muscular dystrophy of mdx mice.

Full Text

Restricted Access

About the authors

A. V Sokolova

Institute of Cytology Russian Academy of Science

Email: avsokolova@inbox.ru

NA. A Timonina

Saint Petersburg State University

V. V Kravtsova

Saint Petersburg State University

I. I Krivoi

Saint Petersburg State University

N. S Skripkina

City clinical hospital № 31

E. V Kaminskaia

Institute of Cytology Russian Academy of Science

V. M Mikhailov

Institute of Cytology Russian Academy of Science

References

  1. Min Y.L., Bassel-Duby R., Olson E.N. CRISPR Correction of Duchenne Muscular Dystrophy. Ann. Rev. Med. 2019; 70: 239-55.
  2. Collins C.A., Morgan J.E. Duchenne's muscular dystrophy: animal models used to investigate pathogenesis and develop therapeutic strategies. Int. J. Exp. Pathol. 2003; 84(4): 165-72.
  3. Dalkilic I., Kunkel L.M. Muscular dystrophies: genes to pathogenesis. Curr. Opin. Genet. Dev. 2003; 13(3): 231-8.
  4. Otto A., Coolins-Hooper H., Patel K. The origin, molecurlar regulation and therapeutic potencial of myogenic stem cell populations. J. of Anatomy 2009; 215: 477-97.
  5. Negroni E., Gidaro T., Bigot A. et al. Stem cells and muscle diseases: advances in cell therapy strategies. J. Neuropathology and Applied Neurobiology 2015; 41: 270-87.
  6. Hoffman E.P., Brown R.H. Jr., Kunkel L.M. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 1987; 51(6): 919-28.
  7. Зайнитдинова М.И., Смирнихина С.А., Лавров А.В. и др. Геннотерапевтические подходы к лечению миодистрофии Дюшенна. Гены & Клетки 2019; XIV(4): 6-18.
  8. Bulfield G., Siller W.G., Wight P.A. et al. X chromosome-linked muscular dystrophy (mdx) in the mouse. PNAS USA 1984; 81(4): 1189-92.
  9. Sicinski P., Geng Y., Ryder-Cook A.S. et al. The molecular basis of muscular dystrophy in the mdx mouse: a point mutation. Science 1989; 244(4912): 1578-80.
  10. Kong J., Anderson J.E. Dystrophin is required for organizing large acetylcholine receptor aggregates. Brain Res. 1999; 839(2): 298-304.
  11. Minatel E., Neto H.S., Marques M.J. Acetylcholine receptors and neuronal nitric oxide synthase distribution at the neuromuscular junction of regenerated muscle fibers. Muscle Nerve 2001; 24: 410-6.
  12. Marques M.J., Pertille A., Carvalho C.L. et al. Acetylcholine receptor organization at the dystrophic extraocular muscle neuromuscular junction. Anat. Rec. (Hoboken) 2007; 290(7): 846-54.
  13. Соколова А.В., Зенин В.В., Михайлов В.М. Структура нейро-мышечных соединений и дифференцировка поперечно-полосатых мышечных волокон у мышей mdx после клеточной терапии стволовыми клетками костного мозга. Цитология 2010; 52(5): 399-406.
  14. Quaеttrocelli M., Cassano M., Crippa S. et al. Cell therapy strategies and improvements for muscular dystrophy. Cell Death and Differentiation 2010; 17: 1222-9.
  15. Wilschut K.J., Ling V.B., Bernstein H.S. Concise Review: Stem cell therapy for muscular dystrophies. Stem Cells Translational medicine 2012; 1(11): 833-42.
  16. Partridge T.A., Morgan J.E., Coulton G.R. et al. Conversion of mdx myofibres from dystrophin-negative to -positive by injection of normal myoblasts. Nature 1989; 337: 176-9.
  17. Siemionow M., Cwykiel J., Heydemann A. et al. Dystrophin expressing chimeric (DEC) human cells provide a potencial therapy for Duchenne muscular therapy. Stem Cell Reviews and reports 2018; 14: 370-84.
  18. Gussoni E., Soneoka Y., Strickland C.D. et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 1999; 401(6751): 390-4.
  19. Bittner R.E., Schofer C., Weipoltshammer K. et al. Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice. Anat. Embryol. (Berl.) 1999; 199(5): 391-6.
  20. 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. The Journal of Cell Biology 1999; 147(4): 869-77.
  21. Torrente Y., Belicchi M., Sampaolesi M. et al. Human circulating AC133(+) stem cells restore dystrophin expression and ameliorate function in dystrophic skeletal muscle. J. Clin. Invest. 2004; 114: 182-95.
  22. Peault B., Rudnicki M., Torrente Y. et al. Stem and progenitor cells in skeletal muscle development, maintenance, and therapy. Mol. Ther. 2007; 15(5): 867-77.
  23. Galvez B.G., Sampaolesi M., Brunelli S. et al. Complete repair of dystrophic skeletal muscle by mesoangioblasts with enhanced migration ability. J. Cell Biol. 2006; 174(2): 231-43.
  24. Dellavalle A., Sampaolesi M., Tonlorenzi R. et al. Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells. Nat. Cell Biol. 2007; 9(3): 255-67.
  25. Farini A., Razini P., Erratico S. et al. Cell based therapy for Duchenne muscular dystrophy. J. Cell. Physiol. 2009; 221(3): 526-34.
  26. Szade K., Gulati G.S., Chan C.K.F. et al. Where hematopoietic stem cells live: The bone marrow niche. Antioxid. Redox Signal. 2018; 29(2): 191-204.
  27. Asahara T., Murohara T. Sullivan A. et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275: 964-7.
  28. Kataoka K., Medina R.J., Kageyama T. et al. Participation of adult mouse bone marrow cells in reconstitution of skin. Am. J. Pathol. 2003; 163(4): 1227-31.
  29. Kale S., Karihaloo A., Clark P.R. et al. Bone marrow stem cells contribute to repair of the ischemically injured renal tubule. J. Clin. Invest. 2003; 112(1): 42-9.
  30. Hess D., Li L., Martin M. et al. Bone marrow-derived stem cells initiate pancreatic regeneration. Nat. Biotechnol. 2003L; 21(7): 763-70.
  31. Mezey E., Chandross K.J. Bone marrow: a possible alternative source of cells in the adult nervous system. Eur. J. Pharmacol. 2000; 405(1-3): 297-302.
  32. Mikhailov V.M. Life cycle of decidual cells. In: Jeon K.W., editor. A survey of cell biology. San Diego: Academic Press (an Elsevier Imprint); 2003. p. 2-63.
  33. Mikhailov V.M., Sokolova A.V., Serikov V.B. et al. Bone marrow stem cells repopulate thyroid regeneration in mice. Pathophysiology 2012; 19: 5-11.
  34. Alawadhi F., Du H., Cakmak H. et al. Bone Marrow-Derived Stem Cell (BMDSC) transplantation improves fertility in a murine model of Asher-man's syndrome. PLoS One 2014; 9(5): e96662.
  35. Ferrari G., Cusella-De Angelis G., Coletta M. et al. Muscle regeneration by bone marrow-derived myogenic progenitors. Science 1998; 279(5356): 1528-30.
  36. LaBarge M.A., Blau H.M. Biological progression from adult bone marrow to mononucleate muscle stem cell to multinucleate muscle fiber in response to injury. Cell 2002; 111(4): 589-601.
  37. Dreyfus P.A., Chretien F., Chazaud B. et al. Adult bone marrow-derived stem cells in muscle connective tissue and satellite cell niches. Am. J. Pathol. 2004; 164(3): 773-9.
  38. Михайлов В.М., Евтифеева Е.В., Сериков В.Б. и др. Участие стволовых клеток костного мозга в дифференцировке поперечнополосатых мышц мышей mdx. Цитология 2006; 48(5): 410-7.
  39. Wernig G., Jansen V., Schafer R. et al. The vast majority of bone-marrow-derived cells integrated into mdx muscle fibers are silent despite long-term engraftment.PNAS USA 2005; 102(33): 11852-7.
  40. Соколова А.В., Соколов Г.В., Михайлов В.М. Слабое комбинированное магнитное поле, настроенное на ион-параметрический резонанс для Ca2+, интенсифицирует синтез дистрофина в скелетных мышцах мышей mdx после клеточной терапии. Цитология 2016; 58 (2):150-5.
  41. Lucarelli G., Isgro A., Sodani P. et al. Hematopoietic stem cell transplantation in thalassemia and sickle cell anemia. Cold Spring Harb. Perspect. Med. 2012; 2(5): a011825.
  42. Hsieh M.M. A standard nonmyeloablative transplantation regimen for adults with sickle cell disease: Are we there Yet? Biol. blood marrow transplantation 2016; 22: 397-9.
  43. Полак Дж., Ван Норден С. Введение в иммуноцитохимию: современные методы и проблемы: Пер. с англ. Москва [СССР]: Мир; 1987
  44. Marques M.J., Taniguti A.P., Minatel E. et al. Nerve terminal contributes to acetylcholine receptor organization at the dystrophic neuromuscular junction of mdx mice. Anat. Rec. (Hoboken) 2007; 290(2): 181-7.
  45. Кравцова В.В., Михайлов В.М., Соколова А.В. и др. Восстановление электрогенеза скелетной мышцы после клеточной терапии миодистрофии у мышей mdx. Доклады Академии наук 2011; 441(2): 272-4.
  46. Mikhailov V.M., Sokolova A.V., Kravtsova V.V. et al. Non-myeloablative bone marrow stem cell transplantation for mdx mice myodystrophy therapy. J. Cell Sci. Ther. 2012; 3: 122.
  47. Соколова А.В. Усиление синтеза дистрофина и улучшение структуры нейромышечных соединений мутантных мышей mdx после трансплантации клеток костного мозга. В: Яблонский П.К., главный редактор. Фундам. наука клин. мед. Материалы XVI Всероссийской медико-биологической конференции молодых ученых (с международным участием); 2013 апрель 20; Санкт-Петербург, Россия. Санкт-Петербург: Издательский дом СПбГУ; 2013. стр. 379-80.
  48. Тимонина Н.А., Кравцова В.В., Михайлова Е.В. и др. Электрогенез концевых пластинок диафрагмы мышей mdx: эффект клеточной терапии. Вестник СПбГУ Сер. 3. 201 5; 3: 66-74
  49. Andrade J., Ge S., Symbatyan G. et al. Effects of sublethal irradiation on patterns of engraftment after murine bone marrow transplantation. Biol. Blood Marrow Transplant. 2011; 17(5): 608-19.
  50. Haddix S.G., Lee Y.I., Kornegay J.N. et al. Cycles of myofiber degeneration and regeneration lead to remodeling of the neuromuscular junction in two mammalian models of Duchenne muscular dystrophy. PLoS One 2018; 13(10): e0205926.
  51. Rafael J.A., Townsend E.R., Squire S.E. et al. Dystrophin and utrophin influence fiber type composition and post-synaptic membrane structure. Hum. Mol. Genet. 2000; 9: 1357-67.
  52. Banks G.B., Chamberlain J.S., Froehner S.C. Truncated dystrophins can influence neuromuscular synapse structure. Mol. Cell. Neurosci. 2009; 40: 433-41.
  53. Kong J., Yang L., Li Q. et al. The absence of dystrophin rather than muscle degeneration causes acetylcholine receptor cluster defects in dystrophic muscle. Neuroreport 2012; 23(2): 82-7.
  54. McClive P.J., Huang D., Morahan G. C57BL/6 and C57BL/10 inbred mouse strains differ at multiple loci on chromosome 4. Immunogenetics 1994; 39: 286-8.
  55. Kennelly K.P., Holmes T.M., Wallace D.M. et al. Early subretinal allograft rejection is characterized by innate immune activity. Cell Transplant. 2017; 26(6): 983-1000.
  56. Sampaolesi M., Blot S., D'Antona G. et al. Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs. Nature 2006; 444(7119): 574-9.
  57. van Putten M., Hulsker M., Young C. et al. Low dystrophin levels increase survival and improve muscle pathology and function in dystrophin/ utrophin double-knockout mice. FASEB J. 2013; 27(6): 2484-95.
  58. van der Pijl E.M., van Putten M., Niks E.H. et al. Low dystrophin levels are insufficient to normalize the neuromuscular synaptic abnormalities of mdx mice. Neuromuscul. Disord. 2018; 28(5): 427-42.
  59. Wells D.J. What is the level of dystrophin expression required for effective therapy of Duchenne muscular dystrophy? J. Muscle Res. Cell Motil. 2019; 40(2): 141-50.
  60. Ozdogu H., Boga C. Hematopoietic stem cell transplantation in adult sickle cell disease: problems and solution. Turk. J. Haematol. 2015; 32(3): 195-205.
  61. Pietzner J., Baer P.C., Duecker R.P. et al. Bone marrow transplantation improves the outcome of Atm-deficient mice through the migration of ANM-competent cells. Human mol. Genetics 2013, 22(3): 493-507

Copyright (c) 2020 Eco-Vector


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: ПИ № ФС 77 - 85657 от 21.07.2023 от 11.03.2014.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies