Embryonic stem (ES) cells are regarded with great promise for future treatment of congenital disease. The well-known capacity of these cells to differentiate into a broad spectrum of cell types makes them highly attractive for their use in the emerging era of regenerative medicine, as they can potentially regenerate every tissue of the body. It has previously been shown that by injecting normal mouse ES cells into early mouse embryos that harbor a mutation, the embryos that do not receive ES cell treatment develop a disease that recapitulates a human disease. As the ES cells are derived from blastocysts, injection of normal ES cells into mutant blastocysts results in a mutual recognition without rejection. As a result of the injection of normal ES cells, the developing animal will be composed of normal cells (derived from the ES cells) and mutant cells (derived from the blastocysts). This approach was applied to determine whether partial restoration of dystrophin in all tissues could lead to global corrections in the mdx dystrophin deficient mouse model. Dr. Elizabeth Stillwell and colleagues created chimeric mice by injecting wild type (WT) LacZ-marked mouse embryonic stem cells into mdx blastocysts, which are predisposed to develop symptoms of Duchenne muscular dystrophy. The resultant animals were then allowed to go to term and become adults. Chimeric mice containing 20% of muscle derived from the normal ES cells and 80% of the muscle derived from the mdx blastocysts (without dystrophin) were selected (WT/mdx). Surprisingly, the muscle had no signs of muscular dystrophy, as the fibers were not necrotic or regenerative. Moreover, molecular markers of muscular dystrophy were absent in the chimeras. Most of the fibers contained dystrophin, despite the fact that the animals contained only 20% of incorporated ES cells. Thus, the structural protein dystrophin spread throughout the muscle. Some portions of the muscle that were not composed of ES-derived cells and therefore did not contain dystrophin were also normal. Importantly, only a small fraction of ES cells incorporated into the mdx muscle during early development is sufficient to rescue muscular dystrophy.


Références : PLoS ONE. 2009;4(3):e4759.