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

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Abstract

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 (∼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.

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

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Publication details

The article was received on 03 Jun 2017, accepted on 07 Jul 2017 and first published on 07 Jul 2017


Article type: Paper
DOI: 10.1039/C7BM00489C
Citation: Biomater. Sci., 2017, Advance Article
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    Spatiotemporal presentation of exogenous SDF-1 with PLGA nanoparticles modulates SDF-1/CXCR4 signaling axis in the rodent cortex

    D. Dutta, K. Hickey, M. Salifu, C. Fauer, C. Willingham and S. E. Stabenfeldt, Biomater. Sci., 2017, Advance Article , DOI: 10.1039/C7BM00489C

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