Tags

Type your tag names separated by a space and hit enter

CD133+ cells derived from skeletal muscles of Duchenne muscular dystrophy patients have a compromised myogenic and muscle regenerative capability.
Stem Cell Res. 2018 07; 30:43-52.SC

Abstract

Cell-mediated gene therapy is a possible means to treat muscular dystrophies like Duchenne muscular dystrophy. Autologous patient stem cells can be genetically-corrected and transplanted back into the patient, without causing immunorejection problems. Regenerated muscle fibres derived from these cells will express the missing dystrophin protein, thus improving muscle function. CD133+ cells derived from normal human skeletal muscle contribute to regenerated muscle fibres and form muscle stem cells after their intra-muscular transplantation into an immunodeficient mouse model. But it is not known whether CD133+ cells derived from DMD patient muscles have compromised muscle regenerative function. To test this, we compared CD133+ cells derived from DMD and normal human muscles. DMD CD133+ cells had a reduced capacity to undergo myogenic differentiation in vitro compared with CD133+ cells derived from normal muscle. In contrast to CD133+ cells derived from normal human muscle, those derived from DMD muscle formed no satellite cells and gave rise to significantly fewer muscle fibres of donor origin, after their intra-muscular transplantation into an immunodeficient, non-dystrophic, mouse muscle. DMD CD133+ cells gave rise to more clones of smaller size and more clones that were less myogenic than did CD133+ cells derived from normal muscle. The heterogeneity of the progeny of CD133+ cells, combined with the reduced proliferation and myogenicity of DMD compared to normal CD133+ cells, may explain the reduced regenerative capacity of DMD CD133+ cells.

Authors+Show Affiliations

Dubowitz Neuromuscular Centre, Molecular Neurosciences Section, Developmental Neuroscience Programme, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK; NIHR Great Ormond Street Hospital Biomedical Research Centre, 30 Guilford Street, London WC1N 1EH, UK.Dubowitz Neuromuscular Centre, Molecular Neurosciences Section, Developmental Neuroscience Programme, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK; NIHR Great Ormond Street Hospital Biomedical Research Centre, 30 Guilford Street, London WC1N 1EH, UK.Dubowitz Neuromuscular Centre, Molecular Neurosciences Section, Developmental Neuroscience Programme, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK; NIHR Great Ormond Street Hospital Biomedical Research Centre, 30 Guilford Street, London WC1N 1EH, UK. Electronic address: jennifer.morgan@ucl.ac.uk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29783100

Citation

Meng, Jinhong, et al. "CD133+ Cells Derived From Skeletal Muscles of Duchenne Muscular Dystrophy Patients Have a Compromised Myogenic and Muscle Regenerative Capability." Stem Cell Research, vol. 30, 2018, pp. 43-52.
Meng J, Muntoni F, Morgan J. CD133+ cells derived from skeletal muscles of Duchenne muscular dystrophy patients have a compromised myogenic and muscle regenerative capability. Stem Cell Res. 2018;30:43-52.
Meng, J., Muntoni, F., & Morgan, J. (2018). CD133+ cells derived from skeletal muscles of Duchenne muscular dystrophy patients have a compromised myogenic and muscle regenerative capability. Stem Cell Research, 30, 43-52. https://doi.org/10.1016/j.scr.2018.05.004
Meng J, Muntoni F, Morgan J. CD133+ Cells Derived From Skeletal Muscles of Duchenne Muscular Dystrophy Patients Have a Compromised Myogenic and Muscle Regenerative Capability. Stem Cell Res. 2018;30:43-52. PubMed PMID: 29783100.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CD133+ cells derived from skeletal muscles of Duchenne muscular dystrophy patients have a compromised myogenic and muscle regenerative capability. AU - Meng,Jinhong, AU - Muntoni,Francesco, AU - Morgan,Jennifer, Y1 - 2018/05/12/ PY - 2017/10/30/received PY - 2018/05/03/revised PY - 2018/05/10/accepted PY - 2018/5/22/pubmed PY - 2019/2/9/medline PY - 2018/5/22/entrez KW - CD133+ cells KW - DMD KW - Muscle regeneration KW - Muscle stem cells SP - 43 EP - 52 JF - Stem cell research JO - Stem Cell Res VL - 30 N2 - Cell-mediated gene therapy is a possible means to treat muscular dystrophies like Duchenne muscular dystrophy. Autologous patient stem cells can be genetically-corrected and transplanted back into the patient, without causing immunorejection problems. Regenerated muscle fibres derived from these cells will express the missing dystrophin protein, thus improving muscle function. CD133+ cells derived from normal human skeletal muscle contribute to regenerated muscle fibres and form muscle stem cells after their intra-muscular transplantation into an immunodeficient mouse model. But it is not known whether CD133+ cells derived from DMD patient muscles have compromised muscle regenerative function. To test this, we compared CD133+ cells derived from DMD and normal human muscles. DMD CD133+ cells had a reduced capacity to undergo myogenic differentiation in vitro compared with CD133+ cells derived from normal muscle. In contrast to CD133+ cells derived from normal human muscle, those derived from DMD muscle formed no satellite cells and gave rise to significantly fewer muscle fibres of donor origin, after their intra-muscular transplantation into an immunodeficient, non-dystrophic, mouse muscle. DMD CD133+ cells gave rise to more clones of smaller size and more clones that were less myogenic than did CD133+ cells derived from normal muscle. The heterogeneity of the progeny of CD133+ cells, combined with the reduced proliferation and myogenicity of DMD compared to normal CD133+ cells, may explain the reduced regenerative capacity of DMD CD133+ cells. SN - 1876-7753 UR - https://www.unboundmedicine.com/medline/citation/29783100/CD133+_cells_derived_from_skeletal_muscles_of_Duchenne_muscular_dystrophy_patients_have_a_compromised_myogenic_and_muscle_regenerative_capability_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1873-5061(18)30122-3 DB - PRIME DP - Unbound Medicine ER -