Abstract
Three populations of muscle-derived cells (PP1, PP3, and PP6) were isolated from mouse skeletal muscle using modified preplate technique and retrovirally transduced with BMP4/GFP. In vitro, the PP1 cells (fibroblasts) proliferated significantly slower than the PP3 (myoblasts) and PP6 cells (muscle-derived stem cells); the PP1 and PP6 cells showed a superior rate of survival compared with PP3 cells under oxidative stress; and the PP6 cells showed significantly superior chondrogenic capabilities than PP1 and PP3 cells. In vivo, the PP6 cells promoted superior cartilage regeneration compared with the other muscle-derived cell populations. The cartilage defects in the PP6 group had significantly higher histological scores than those of the other muscle-derived cell groups, and GFP detection revealed that the transplanted PP6 cells showed superior in vivo cell survival and chondrogenic capabilities compared with the PP1 and PP3 cells. PP6 cells (muscle-derived stem cells) are superior to other primary muscle-derived cells for use as a cellular vehicle for BMP4-based ex vivo gene therapy to heal full-thickness osteo-chondral defects. The superiority of the PP6/muscle-derived stem cells appears to be attributable to a combination of increased rate of in vivo survival and superior chondrogenic differentiation capacity.
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