title: The influence of sex on the chondrogenic potential of muscle-derived stem cells: implications for cartilage regeneration and repair.
abstract: OBJECTIVE
  To explore possible differences in muscle-derived stem cell (MDSC) chondrogenic differentiation in vitro and articular cartilage regeneration in vivo between murine male MDSCs (M-MDSCs) and female MDSCs (F-MDSCs).
  
  
  METHODS
  Three different populations of M- and F-MDSCs (n = 3 of each sex) obtained via preplate technique, which separates cells based on their variable adhesion characteristics, were compared for their in vitro chondrogenic potential using pellet culture. Cells were assayed with and without retroviral transduction to express bone morphogenetic protein 4 (BMP-4). The influence of both expression of stem cell marker Sca1 and in vitro expansion on the chondrogenic potential of M- and F-MDSCs was also determined. Additionally, BMP-4-transduced M- and F-MDSCs were applied to a full-thickness articular cartilage defect (n = 5 each) on the femur of a nude rat, and the quality of the repaired tissue was evaluated by macroscopic and histologic examination.
  
  
  RESULTS
  With and without BMP-4 gene transduction, M-MDSCs produced significantly larger pellets with a richer extracellular matrix, compared with F-MDSCs. Sca1 purification influenced the chondrogenic potential of MDSCs, especially M-MDSCs. Long-term culture did not affect the chondrogenic potential of M-MDSCs but did influence F-MDSCs. M-MDSCs repaired articular cartilage defects more effectively than did F-MDSCs at all time points tested, as assessed both macroscopically and histologically.
  
  
  CONCLUSIONS
  Our findings demonstrate that sex influences the chondrogenic differentiation and articular cartilage regeneration potential of MDSCs. Compared with female MDSCs, male MDSCs display more chondrogenic differentiation and better cartilage regeneration potential.
authors.affiliation: Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213-2582, USA.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Seiji
authors.initials: S
authors.lastname: Kubo
authors.forename: Laura B
authors.initials: LB
authors.lastname: Meszaros
authors.forename: Karin A
authors.initials: KA
authors.lastname: Corsi
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Cooper
authors.forename: Guangheng
authors.initials: G
authors.lastname: Li
authors.forename: Arvydas
authors.initials: A
authors.lastname: Usas
authors.forename: Aki
authors.initials: A
authors.lastname: Osawa
authors.forename: Freddie H
authors.initials: FH
authors.lastname: Fu
authors.forename: Johnny
authors.initials: J
authors.lastname: Huard
mesh_terms: D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics; D002356:Cartilage / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010003:Osteoarthritis / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D011923:Rats, Nude; D012038:Regeneration / Q000502:physiology; D012727:Sex Characteristics; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods; D014161:Transduction, Genetic
chemical_list: D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; C000593751:Atxn1 protein, rat; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins