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.
Highlights
CD133+ cells are a rare population that resides within human skeletal muscle (Benchaouir et al, 2007; Meng et al, 2014; Negroni et al, 2009)
We and others have shown that CD133+ cells isolated from normal human muscle contribute to muscle regeneration (Negroni et al, 2009) and form functional muscle stem cells after their intramuscular transplantation in an immunodeficient mouse model (Meng et al, 2014), but CD133+ cells derived from DMD patient muscle have not been extensively investigated (Benchaouir et al, 2007; Meng et al, 2014)
We found that human skeletal muscle -derived CD133+ cells are heterogeneous, containing cells of satellite cell/ myoblast, myoendothelial, pericyte and fibroblast lineages
Summary
CD133+ cells are a rare population that resides within human skeletal muscle (Benchaouir et al, 2007; Meng et al, 2014; Negroni et al, 2009). Changes in the components of the stem cell niche (Smith et al, 2016; Alexakis et al, 2007; Sabatelli et al, 2012) (e.g. alterations in components of connective tissue, or of the muscle fibre) or signalling pathways (Jiang et al, 2014) may be deleterious to satellite cell function. It is not known whether any of these factors affect CD133+ cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
