Defective Myoblasts Identified in Duchenne Muscular Dystrophy

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1983 Aug 1

PMID 6576361

Citations 131

Authors

H M Blau

C Webster

G K Pavlath

Affiliations

Soon will be listed here.

Abstract

A defect in the proliferative capacity of satellite cells, mononucleated precursors of mature muscle fibers, was found in clonal analyses of cells cultured from Duchenne muscular dystrophy (DMD) patients. The total yield of myoblasts per gram of muscle biopsy was decreased to 5% of normal. Of the DMD myoblast clones obtained, a large proportion contained a morphological class of flat distended cells that had an increased generation time and ceased to proliferate beyond 100-1,000 cells but could be induced to fuse and form myotubes. The altered muscle phenotype was detected in all cultures from DMD patients but was rarely found among myoblasts of controls. By age 14 yr, it comprised as man as 90% of DMD myoblasts. The remaining DMD myoblast clones, which initially grew well, had severely impaired proliferative capacity upon passage and further cultivation. Eventually all myoblasts from DMD muscle tissue exhibited defective growth potential. In contrast, the fibroblast yield and proliferative capacity from DMD samples did not differ from normal. Based on these findings, we propose a hypothesis for the etiology of DMD: Dividing myoblasts are required for muscle growth and maintenance, and the limited capacity of DMD myoblasts to grow is directly related to the progressive muscle degeneration characteristic of the disease.

Citing Articles

Gene-editing in patient and humanized-mice primary muscle stem cells rescues dysferlin expression in dysferlin-deficient muscular dystrophy.

Escobar H, Di Francescantonio S, Smirnova J, Graf R, Muthel S, Marg A Nat Commun. 2025; 16(1):120.

PMID: 39747848 PMC: 11695731. DOI: 10.1038/s41467-024-55086-0.

Epigenetic control of myogenic identity of human muscle stem cells in Duchenne muscular dystrophy.

Massenet J, Weiss-Gayet M, Bandukwala H, Bouchereau W, Gobert S, Magnan M iScience. 2024; 27(12):111350.

PMID: 39650736 PMC: 11625291. DOI: 10.1016/j.isci.2024.111350.

Interplay between Pitx2 and Pax7 temporally governs specification of extraocular muscle stem cells.

Kuriki M, Korb A, Comai G, Tajbakhsh S PLoS Genet. 2024; 20(6):e1010935.

PMID: 38875306 PMC: 11178213. DOI: 10.1371/journal.pgen.1010935.

AMONDYS 45 (Casimersen), a Novel Antisense Phosphorodiamidate Morpholino Oligomer: Clinical Considerations for Treatment in Duchenne Muscular Dystrophy.

Vasterling M, Maitski R, Davis B, Barnes J, Kelkar R, Klapper R Cureus. 2024; 15(12):e51237.

PMID: 38283433 PMC: 10821770. DOI: 10.7759/cureus.51237.

Regulation of Satellite Cells Functions during Skeletal Muscle Regeneration: A Critical Step in Physiological and Pathological Conditions.

Careccia G, Mangiavini L, Cirillo F Int J Mol Sci. 2024; 25(1).

PMID: 38203683 PMC: 10778731. DOI: 10.3390/ijms25010512.

References

Bischoff R . Enzymatic liberation of myogenic cells from adult rat muscle. Anat Rec. 1974; 180(4):645-61. DOI: 10.1002/ar.1091800410. View

Hauschka S . Clonal analysis of vertebrate myogenesis. 3. Developmental changes in the muscle-colony-forming cells of the human fetal limb. Dev Biol. 1974; 37(2):345-68. DOI: 10.1016/0012-1606(74)90154-7. View

KONIGSBERG U, LIPTON B, KONIGSBERG I . The regenerative response of single mature muscle fibers isolated in vitro. Dev Biol. 1975; 45(2):260-75. DOI: 10.1016/0012-1606(75)90065-2. View

IONASESCU V, ZELLWEGER H, Burmeister L . Detection of carriers and genetic counseling in duchenne muscular dystrophy by ribosomal protein synthesis. Acta Neurol Scand. 1976; 54(5):442-52. DOI: 10.1111/j.1600-0404.1976.tb04376.x. View

Thompson E, Yasin R, van Beers G, Nurse K, Al-Ani S . Myogenic defect in human muscular dystrophy. Nature. 1977; 268(5617):241-3. DOI: 10.1038/268241a0. View

Papayannopoulou T, Brice M, Stamatoyannopoulos G . Hemoglobin F synthesis in vitro: evidence for control at the level of primitive erythroid stem cells. Proc Natl Acad Sci U S A. 1977; 74(7):2923-7. PMC: 431348. DOI: 10.1073/pnas.74.7.2923. View

Golbus M, Stephens J, Mahoney M, Hobbins J, Haseltine F, Caskey C . Failure of fetal creatine phosphokinase as a diagnostic indicator of Duchenne muscular dystrophy. N Engl J Med. 1979; 300(15):860-1. DOI: 10.1056/NEJM197904123001515. View

Papayannopoulou T, Kalmantis T, Stamatoyannopoulos G . Cellular regulation of hemoglobin switching: evidence for inverse relationship between fetal hemoglobin synthesis and degree of maturity of human erythroid cells. Proc Natl Acad Sci U S A. 1979; 76(12):6420-4. PMC: 411876. DOI: 10.1073/pnas.76.12.6420. View

IONASESCU V, IONASESCU R, Feld R, Witte D, CANCILLA P, Kaeding L . Alterations in creatine kinase in fresh muscle and cell cultures in Duchenne dystrophy. Ann Neurol. 1981; 9(4):394-9. DOI: 10.1002/ana.410090413. View

10.

IONASESCU V, Monaco L, Sandra A, IONASESCU R, Burmeister L, Deprosse C . Alterations in lipid incorporation in Duchenne muscular dystrophy. Studies of fresh and cultured muscle. J Neurol Sci. 1981; 50(2):249-51. DOI: 10.1016/0022-510x(81)90171-4. View

11.

Thompson E . Tissue culture of dystrophic muscle cells. Br Med Bull. 1980; 36(2):181-5. DOI: 10.1093/oxfordjournals.bmb.a071635. View

12.

Franklin G, Cavanagh N, Hughes B, Yasin R, Thompson E . Creatine kinase isoenzymes in cultured human muscle cells. I. Comparison of Duchenne muscular dystrophy with other myopathic and neurogenic disease. Clin Chim Acta. 1981; 115(2):179-89. DOI: 10.1016/0009-8981(81)90074-7. View

13.

Cavanagh N, Franklin G, Hughes B, Yasin R, Phillips E, van Beers G . Creatine kinase isoenzymes in cultured human muscle cells. II. A study of carrier females for Duchenne muscular dystrophy by needle and open biopsy. Clin Chim Acta. 1981; 115(2):191-8. DOI: 10.1016/0009-8981(81)90075-9. View

14.

Blau H, Webster C . Isolation and characterization of human muscle cells. Proc Natl Acad Sci U S A. 1981; 78(9):5623-7. PMC: 348807. DOI: 10.1073/pnas.78.9.5623. View

15.

Blau H, Webster C, Chiu C, GUTTMAN S, Chandler F . Differentiation properties of pure populations of human dystrophic muscle cells. Exp Cell Res. 1983; 144(2):495-503. DOI: 10.1016/0014-4827(83)90431-7. View

16.

Mauro A . Satellite cell of skeletal muscle fibers. J Biophys Biochem Cytol. 1961; 9:493-5. PMC: 2225012. DOI: 10.1083/jcb.9.2.493. View

17.

STOCKDALE F, Holtzer H . DNA synthesis and myogenesis. Exp Cell Res. 1961; 24:508-20. DOI: 10.1016/0014-4827(61)90450-5. View

18.

OSteen W . THE GROWTH OF HUMAN DYSTROPHIC SKELETAL MUSCLE IN DIFFUSION CHAMBERS. Tex Rep Biol Med. 1963; 21:369-79. View

19.

Okazaki K, Holtzer H . Myogenesis: fusion, myosin synthesis, and the mitotic cycle. Proc Natl Acad Sci U S A. 1966; 56(5):1484-90. PMC: 220007. DOI: 10.1073/pnas.56.5.1484. View

20.

Brooke M, Engel W . The histographic analysis of human muscle biopsies with regard to fiber types. 4. Children's biopsies. Neurology. 1969; 19(6):591-605. DOI: 10.1212/wnl.19.6.591. View