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Publication : Spatiotemporal presentation of exogenous SDF-1 with PLGA nanoparticles modulates SDF-1/CXCR4 signaling axis in the rodent cortex.

First Author  Dutta D Year  2017
Journal  Biomater Sci Volume  5
Issue  8 Pages  1640-1651
PubMed ID  28703822 Mgi Jnum  J:268860
Mgi Id  MGI:6272477 Doi  10.1039/c7bm00489c
Citation  Dutta D, et al. (2017) Spatiotemporal presentation of exogenous SDF-1 with PLGA nanoparticles modulates SDF-1/CXCR4 signaling axis in the rodent cortex. Biomater Sci 5(8):1640-1651
abstractText  Stromal cell-derived factor-1 (SDF-1) and its key receptor CXCR4 have been implicated in directing cellular recruitment for several pathological/disease conditions thus also gained considerable attention for regenerative medicine. One regenerative approach includes sustained release of SDF-1 to stimulate prolonged stem cell recruitment. However, the impact of SDF-1 sustained release on the endogenous SDF-1/CXCR4 signaling axis is largely unknown as auto-regulatory mechanisms typically dictate cytokine/receptor signaling. We hypothesize that spatiotemporal presentation of exogenous SDF-1 is a key factor in achieving long-term manipulation of endogenous SDF-1/CXCR4 signaling. Here in the present study, we sought to probe our hypothesis using a transgenic mouse model to contrast the spatial activation of endogenous SDF-1 and CXCR4 in response to exogenous SDF-1 injected in bolus or controlled release (PLGA nanoparticles) form in the adult rodent cortex. Our data suggests that the manner of SDF-1 presentation significantly affected initial CXCR4 cellular activation/recruitment despite having similar protein payloads over the first 24 h ( approximately 30 ng for both bolus and sustained release groups). Yet, one week post-injection, this response was negligible. Therefore, the transient nature CXCR4 recruitment/activation in response to bolus or controlled release SDF-1 indicated that cytokine/receptor auto-regulatory mechanisms may demand more complex release profiles (i.e. delayed and/or pulsed release) to achieve sustained cellular response.
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