UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Contribution of Human Muscle-Derived Cells to Skeletal Muscle Regeneration in Dystrophic Host Mice

Meng, JH; Adkin, CF; Xu, SW; Muntoni, F; Morgan, JE; (2011) Contribution of Human Muscle-Derived Cells to Skeletal Muscle Regeneration in Dystrophic Host Mice. PLOS ONE , 6 (3) , Article e17454. 10.1371/journal.pone.0017454. Green open access

[img]
Preview
PDF
1301408.pdf

Download (1MB)

Abstract

Background: Stem cell transplantation is a promising potential therapy for muscular dystrophies, but for this purpose, the cells need to be systemically-deliverable, give rise to many muscle fibres and functionally reconstitute the satellite cell niche in the majority of the patient's skeletal muscles. Human skeletal muscle-derived pericytes have been shown to form muscle fibres after intra-arterial transplantation in dystrophin-deficient host mice. Our aim was to replicate and extend these promising findings.Methodology/Principal Findings: Isolation and maintenance of human muscle derived cells (mdcs) was performed as published for human pericytes. Mdscs were characterized by immunostaining, flow cytometry and RT-PCR; also, their ability to differentiate into myotubes in vitro and into muscle fibres in vivo was assayed. Despite minor differences between human mdcs and pericytes, mdscs contributed to muscle regeneration after intra-muscular injection in mdx nu/nu mice, the CD56+ sub-population being especially myogenic. However, in contrast to human pericytes delivered intra-arterially in mdx SCID hosts, mdscs did not contribute to muscle regeneration after systemic delivery in mdx nu/nu hosts.Conclusions/Significance: Our data complement and extend previous findings on human skeletal muscle-derived stem cells, and clearly indicate that further work is necessary to prepare pure cell populations from skeletal muscle that maintain their phenotype in culture and make a robust contribution to skeletal muscle regeneration after systemic delivery in dystrophic mouse models. Small differences in protocols, animal models or outcome measurements may be the reason for differences between our findings and previous data, but nonetheless underline the need for more detailed studies on muscle-derived stem cells and independent replication of results before use of such cells in clinical trials.

Type: Article
Title: Contribution of Human Muscle-Derived Cells to Skeletal Muscle Regeneration in Dystrophic Host Mice
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0017454
Publisher version: http://dx.doi.org/10.1371/journal.pone.0017454
Language: English
Additional information: © 2011 Meng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was supported by the International Collaborative Effort for DMD (ICE), the Wellcome Trust (http://www.wellcome.ac.uk/) grant number 084241/Z/07/Z, and the Medical Research Council (http://www.mrc.ac.uk/index.htm) grant number G0900872. J.M. was funded by the International Collaborative Effort for DMD (ICE) and the Medical Research Council, and J.E.M. holds a Wellcome Trust University award. J.E.M. and F.M. are PIs of the MRC Centre for Neuromuscular Diseases. C.A. was funded by the Duchenne Parent Project, Netherlands. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: MESENCHYMAL STEM-CELLS, HUMAN MYOBLAST TRANSPLANTATION, ENDOTHELIAL PROGENITOR CELLS, DUCHENNE MUSCULAR-DYSTROPHY, SIDE POPULATION CELLS, SATELLITE CELLS, MYOGENIC DIFFERENTIATION, SELF-RENEWAL, MDX MOUSE, IN-VITRO
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1301408
Downloads since deposit
95Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item