The influence of sex on the chondrogenic potential of muscle-derived stem cells: implications for cartilage regeneration and repair.
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.
Matsumoto
Tomoyuki
T
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213-2582, USA.
Kubo
Seiji
S
Meszaros
Laura B
LB
Corsi
Karin A
KA
Cooper
Gregory M
GM
Li
Guangheng
G
Usas
Arvydas
A
Osawa
Aki
A
Fu
Freddie H
FH
Huard
Johnny
J
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
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