Regulating in Vitro Motility of Human Mesenchymal Stem Cells with Macrophage Migration Inhibitory Factor (MIF) and a Small-Molecule MIF Antagonist

  • Kim C. O’Connor
  • Bonnie L. Barrilleaux
  • Donald G. Phinney
  • Benjamin W. Fischer-Valuck
  • Katie C. Russell
  • Darwin J. Prockop
Conference paper
Part of the ESACT Proceedings book series (ESACT, volume 5)

Abstract

Human mesenchymal stem cells (MSCs) from bone marrow possess a remarkable capacity to home to and regenerate damaged tissue, but the molecular mechanisms governing their migration and homing are not well defined. The present study reveals that a potent pro-inflammatory cytokine, macrophage migration inhibitory factor (MIF), regulates in vitro chemokinesis of MSCs in a dose-dependent manner, inhibiting approximately 50% of migration at 100 ng/ml recombinant MIF. The small-molecule MIF antagonist (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1, 500 μg/μg rMIF) restores MSC migration to levels found in the absence of MIF. ISO-1 (85 μg/ml) increases migration to conditioned medium containing MIF from bronchial epithelial cells by ≥ 3-fold for a variety of donor MSC preparations (p < 0.05). Regulation of MIF signaling may be an effective method to control the innate homing response of MSCs and improve the efficacy of MSC therapies for injured lung and other damaged tissues.

Keywords

Migration Inhibitory Factor Migration Inhibitory Factor Expression Acetic Acid Methyl Ester Stem Cell Growth Medium Recombinant Migration Inhibitory Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported by a grant from the National Science Foundation (BES-0514242).

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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Kim C. O’Connor
    • 1
  • Bonnie L. Barrilleaux
    • 1
  • Donald G. Phinney
    • 2
  • Benjamin W. Fischer-Valuck
    • 1
  • Katie C. Russell
    • 1
  • Darwin J. Prockop
    • 3
  1. 1.Department of Chemical and Biomolecular Engineering and Tulane Center for Gene TherapyTulane UniversityNew OrleansUSA
  2. 2.Department of Molecular TherapeuticsThe Scripps Research InstituteJupiterUSA
  3. 3.Department of Molecular and Cellular Medicine, College of MedicineTexas A&M Health Science CenterTempleUSA

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