Homing therapy

Skeletal muscle can be repaired by a class of stem cells known as mesangioblasts, which reside within blood vessels. Injection of mesoangioblasts into the femoral artery of mice improves muscle function in a mouse model of muscular dystrophy. Only a small fraction of the injected cells enters the tissue after injection, however. With their new findings, the authors report how to increase this fraction.

The authors found that mesoangioblasts efficiently crossed endothelium-coated filters in vitro when the other side held either mature myotubes or muscle-associated cytokines, such as SDF-1. Immature myoblasts, which secrete less of these cytokines, did not induce strong migration.

In addition to cytokines, adhesion molecules also improved migration. Transfection of mesoangioblasts with L-selectin or α4 integrin increased the cells' migration efficiency across the endothelium-coated filters. L-selectin and α4 integrin are not normally expressed by mesangioblasts, but are known to help leukocytes migrate through vessels walls into nearby tissues.

In vivo experiments demonstrated that both strategies improved the stem cells' homing ability in a mouse model of muscular dystrophy. When cytokine-pretreated cells were injected in the femoral artery, ∼20% of the cells migrated to the thigh muscle, compared with 10% of untreated control cells. A similar improvement was detected for α4 integrin–expressing stem cells.

Both modifications together made an even better improvement. Approximately 50% of the mesoangioblasts that were pretreated with SDF-1 and that expressed α4 integrin entered the muscle.

After receiving the juiced-up stem cells, the mice had improved muscle function. Galvez et al. are now testing the same strategy in a dog model of muscular dystrophy. Moreover, they hypothesize that, with the right cytokines, a similar experimental approach could be used to improve the homing ability of other stem cell types.