Homing therapy

The BDNF-induced increase (left) in synapses (red) on a neuron (green) is lost if í µí»ƒ-catenin and cadherin are locked together (right). S tem cells become much more effi cient at muscle repair if they fi rst get a boost of cytokines and migratory adhesion molecules, report Galvez et al. (page 231). The improved repair stems from better homing abilities. 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 fi ndings, the authors report how to increase this fraction. The authors found that mesoangioblasts effi ciently crossed endothelium-coated fi lters 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 effi ciency across the endothelium-coated fi lters. 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, ‫%02ف‬ 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 modifi cations 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. S ynaptic vesicles get dispersed to new sites, according to Bamji et al. on page 289, via neurotrophin-induced disruption of adhesion complexes. The dispersal increases synaptic density, number, and size. Dispersal is triggered by the neurotrophin called brain-derived neurotrophic factor (BDNF), which is produced and secreted by active nerve …