The influence of sex on the chondrogenic potential of muscle-derived stem cells: Implications for cartilage regeneration and repair
Tomoyuki Matsumoto
Children's Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, Pennsylvania
Drs. Matasumoto and Kubo contributed equally to this work.
Search for more papers by this authorSeiji Kubo
Children's Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, Pennsylvania
Drs. Matasumoto and Kubo contributed equally to this work.
Search for more papers by this authorLaura B. Meszaros
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania
Search for more papers by this authorKarin A. Corsi
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania
Search for more papers by this authorGregory M. Cooper
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania
Search for more papers by this authorGuangheng Li
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania
Search for more papers by this authorArvydas Usas
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania
Search for more papers by this authorAki Osawa
Children's Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, Pennsylvania
Search for more papers by this authorFreddie H. Fu
University of Pittsburgh, Pittsburgh, Pennsylvania
Search for more papers by this authorCorresponding Author
Johnny Huard
Children's Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, Pennsylvania
Dr. Huard has received consulting fees from Cook MyoSite, Inc. (more than $10,000).
Children's Hospital of Pittsburgh, 4100 Rangos Research Center, 3705 Fifth Avenue, Pittsburgh, PA 15213-2582Search for more papers by this authorTomoyuki Matsumoto
Children's Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, Pennsylvania
Drs. Matasumoto and Kubo contributed equally to this work.
Search for more papers by this authorSeiji Kubo
Children's Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, Pennsylvania
Drs. Matasumoto and Kubo contributed equally to this work.
Search for more papers by this authorLaura B. Meszaros
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania
Search for more papers by this authorKarin A. Corsi
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania
Search for more papers by this authorGregory M. Cooper
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania
Search for more papers by this authorGuangheng Li
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania
Search for more papers by this authorArvydas Usas
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania
Search for more papers by this authorAki Osawa
Children's Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, Pennsylvania
Search for more papers by this authorFreddie H. Fu
University of Pittsburgh, Pittsburgh, Pennsylvania
Search for more papers by this authorCorresponding Author
Johnny Huard
Children's Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, Pennsylvania
Dr. Huard has received consulting fees from Cook MyoSite, Inc. (more than $10,000).
Children's Hospital of Pittsburgh, 4100 Rangos Research Center, 3705 Fifth Avenue, Pittsburgh, PA 15213-2582Search for more papers by this authorAbstract
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.
Conclusion
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.
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