Torino, Italy -
Hematopoietic stem cells and mesenchymal stem cells are known to more or less find their way to injured tissue. This is one of the reasons why companies such as Osiris can get away with simply intravenously injecting their mesenchymal stem cells and still get potent results. What mediates natural attraction of stem cells to injured tissue? Well on the one hand, ischemia associated with injury results in production of agents such as SDF-1 and VEGF which act as chemokines. On the other hand, platelet released agents such as sphingosine 1 phosphate also have been demonstrated to call stem cells.
How could one increase the ability of stem cells to home to injured tissue? One approach is to implant on the injured tissue a source of chemokines so to enhance migration. This was previously performed in the form of a SDF-1-fibrin patch which had efficacy in an animal model of infarction.
Another approach would be to alter the normal trafficking of injected stem cells. Usually when stem cells are injected intravenously a lot of them get stuck in the lung and liver. The company Cellcyte Genetics has developed a small molecule agent that prevents cells from getting stuck so that more can circulate and have a higher ability to go to target tissue.
A really novel approach was published by Gerasimou et al. (Homing of annexin-labeled stem cells to apoptotic cells. Cell Mol Biol Lett 2008 Oct 6). This group developed a way to bind Annexin-V to mesenchymal stem cells, while not disturbing the mesenchymal stem cell viability or function. For those of you who work in laboratories, you will know that Annexin-V is usually part of the reagents we use to label apoptotic cells, since Annexin-V binds to phosphaditylserine on the apoptotic cell membrane.
The authors demonstrated that the mesenchymal stem cells bearing Annexin-V had a preferential affinity towards apoptotic bovine aortic endothelial cells.
This approach could potentially be used in vivo to make mesenchymal stem cells localize to injured tissue, which by definition has either apoptotic or necrotic cells (usually both).
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