Strategies to Improve Homing of Stem Cells to achieve better Efficacy in Stem Cell Therapy

Abstract

Stem/progenitor cell based therapeutic approach in our daily routine clinical practice, has been<br><br>elusive dream in medical sciences and improve<br><br>ment of stem cell homing as one of major challenges<br><br>in cell therapy programs, has been considered a promising milestone. It has been proved that<br><br>stem/progenitor cells exhibit a homing response to injured tissues/organs, mediated by interactions of<br><br>chemokin<br><br>e receptors expressed on the cells and chemokines secreted by the injured tissue. For<br><br>improvement of directed homing of the cells, many techniques have been developed either to<br><br>engineer stem/progenitor cells with higher amount of chemokine receptors (stem<br><br>cell<br><br>-<br><br>based<br><br>strategies) or to modulate the target tissues to release higher level of the corresponding chemokines<br><br>(target tissue<br><br>based strategies).<br><br>Treatment with chemical compounds, preconditioning of the cells with hypoxia, cytokine and growth<br><br>factor prim<br><br>ing of the cells, genetic modifications, coating of cell surface with antibodies,<br><br>glycoengineering, coating of stem cells with homing ligands by streptavidin linkers are some of<br><br>strategies to increase the ability of stem cells to respond to the migratory s<br><br>timuli. On the other side to<br><br>modulate target sites to be more attractive for stem cells, some strategies like direct injection of<br><br>chemokines, direct transfection of the target tissue with chemokine encoding genes, injection of<br><br>ectopic chemokine expressing<br><br>cells, application of scaffolds, electrical fields and low level laser have<br><br>been introduced. These extensive investigations have provided significant potentials to enhance<br><br>targeted stem/progenitor cells homing. Meanwhile there are still some limitations to<br><br>apply these<br><br>findings in clinics. To overcome these limitations, further studies should be aimed, unveiling the<br><br>molecular and cellular mechanisms underlying endogenous cell trafficking during physiological and<br><br>pathological events like embryogenesis, inflam<br><br>mation, wound healing, or cancer metastasis