The Influence of Sex on the Chrondrogenic Potential of Muscle-Derived Stem Cells

Arthritis & Rheumatism. 2009;58(12):3809-3819. 

Joint cartilage damage that occurs with conditions such as osteoarthritis (OA) is difficult to treat because cartilage lacks blood, nerve and lymph supplies and has a limited capacity to repair itself. The only widely accepted treatment for this type of damage is total knee replacement. Cartilage regeneration using the patient's own cartilage-forming cells has shown only limited promise, but stem cells have played an increasingly important role in regenerative medicine and tissue engineering and recent studies have suggested that they have potential for cartilage regeneration. Muscle-derived stem cells (MDSCs) have been shown to have the ability to form cartilage and could be a novel source for cartilage tissue engineering.

Recent investigations have shown that there are variations in stem cells from animals of different sexes. A new study, published in the December issue of Arthritis & Rheumatism ( ), sought to determine whether there are differences in the cartilage-forming potential of male versus female MDSCs that might influence their use in tissue engineering applications.

Led by Johnny Huard of the University of Pittsburgh, researchers isolated MDSCs from three male and three female mice and tested the cells for cartilage development (chondrogenesis) both in vitro and in vivo. When stimulated by a growth factor (TGFβ3) and a protein (BMP-4) involved in bone formation and growth, they found that both male and female MDSCs began the process leading to the formation of cartilage cells. Even without using the protein that stimulates bone formation this process took place, but that male MDSCs had a more robust response. They also found that male MDSCs maintained their potential to form cartilage in long term cultures, whereas female MDSCs lost this potential as they grew, indicating that male cells maintain a higher rate of self-renewal.

In a further experiment involving 15 rats, the researchers created a cartilage defect in their knee joints and found that treatment with both male and female MDSCs showed some ability to regenerate cartilage, but treatment with the male cells led to better results.

"Sex differences in stem cell treatments for cartilage repair could have great clinical impact," the authors note. "Sex- and age-related differences in OA are well described and considered to be a key aspect of development and discovery of new treatments." The experiments in this study indicate that stem cell sex differences in the healing of cartilage defects could lead to different treatments of OA in men and women.

The authors conclude: "These results further the understanding of the chondrogenic potential of MDSCs and may contribute to the development of new therapeutic strategies for cartilage repair and regeneration."



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