Modulation of mouse macrophage polarization in vitro using IL-4 delivery by osmotic pumps

Jukka Pajarinen, Yasunobu Tamaki, Joseph K. Antonios, Tzu Hua Lin, Taishi Sato, Zhenyu Yao, Michiaki Takagi, Yrjö T. Konttinen, Stuart B. Goodman

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29 Citations (Scopus)

Abstract

Modulation of macrophage polarization is emerging as promising means to mitigate wear particle-induced inflammation and periprosthetic osteolysis. As a model for continuous local drug delivery, we used miniature osmotic pumps to deliver IL-4 in order to modulate macrophage polarization in vitro from nonactivated M0 and inflammatory M1 phenotypes towards a tissue regenerative M2 phenotype. Pumps delivered IL-4 into vials containing mouse bone marrow macrophage (mBMM) media. This conditioned media (CM) was collected at seven day intervals up to four weeks (week 1 to week 4 samples). IL-4 concentration in the CM was determined by ELISA and its biological activity was assayed by exposing M0 and M1 mBMMs to week 1 or week 4 CM. The IL-4 concentration in the CM approximated the mathematically calculated amount, and its biological activity was well retained, as both M0 and M1 macrophages exposed to either the week 1 or week 4 CM assumed M2-like phenotype as determined by qRT-PCR, ELISA, and immunocytochemistry. The results show that IL-4 can be delivered using osmotic pumps and that IL-4 delivered can modulate macrophage phenotype. Results build a foundation for in vivo studies using our previously validated animal models and provide possible strategies to locally mitigate wear particle-induced macrophage activation and periprosthetic osteolysis.

Original languageEnglish
Pages (from-to)1339-1345
Number of pages7
JournalJournal of Biomedical Materials Research - Part A
Volume103
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

All Science Journal Classification (ASJC) codes

  • Ceramics and Composites
  • Biomaterials
  • Biomedical Engineering
  • Metals and Alloys

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    Pajarinen, J., Tamaki, Y., Antonios, J. K., Lin, T. H., Sato, T., Yao, Z., Takagi, M., Konttinen, Y. T., & Goodman, S. B. (2015). Modulation of mouse macrophage polarization in vitro using IL-4 delivery by osmotic pumps. Journal of Biomedical Materials Research - Part A, 103(4), 1339-1345. https://doi.org/10.1002/jbm.a.35278