title: Muscle-derived stem/progenitor cell dysfunction in Zmpste24-deficient progeroid mice limits muscle regeneration.
abstract: BACKGROUND
  Loss of adult stem cell function during aging contributes to impaired tissue regeneration. Here, we tested the aging-related decline in regeneration potential of adult stem cells residing in the skeletal muscle.
  
  
  METHODS
  We isolated muscle-derived stem/progenitor cells (MDSPCs) from progeroid Zmpste24-deficient mice (Zmpste24(-/-)) with accelerated aging phenotypes to investigate whether mutation in lamin A has an adverse effect on muscle stem/progenitor cell function.
  
  
  RESULTS
  Our results indicate that MDSPCs isolated from Zmpste24(-/-) mice show reduced proliferation and myogenic differentiation. In addition, Zmpste24(-/-) MDSPCs showed impaired muscle regeneration, with a limited engraftment potential when transplanted into dystrophic muscle, compared with wild-type (WT) MDSPCs. Exposure of progeroid Zmpste24(-/-) MDSPCs to WT MDSPCs rescued the myogenic differentiation defect in vitro.
  
  
  CONCLUSIONS
  These results demonstrate that adult stem/progenitor cell dysfunction contributes to impairment of tissue regeneration and suggest that factors secreted by functional cells are indeed important for the therapeutic effect of adult stem cells.
authors.forename: Minjung
authors.initials: M
authors.lastname: Song
authors.forename: Mitra
authors.initials: M
authors.lastname: Lavasani
authors.forename: Seth D
authors.initials: SD
authors.lastname: Thompson
authors.forename: Aiping
authors.initials: A
authors.lastname: Lu
authors.forename: Bahar
authors.initials: B
authors.lastname: Ahani
authors.forename: Johnny
authors.initials: J
authors.lastname: Huard
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D018920:Coculture Techniques; D034904:Lamin Type A / Q000378:metabolism; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D010641:Phenotype; D012038:Regeneration; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014184:Transplantation, Homologous
chemical_list: D034904:Lamin Type A; D008565:Membrane Proteins; D008666:Metalloendopeptidases; C491250:Zmpste24 protein, mouse