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, Sarah Stabenfeldt

Research output: Contribution to journalArticle

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1640-1651
Number of pages12
JournalBiomaterials Science
Volume5
Issue number8
DOIs
StatePublished - Aug 1 2017

ASJC Scopus subject areas

  • Biomedical Engineering
  • Materials Science(all)

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