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Spotlight on Stem Cell Homing and Mobilisation

A novel perspective on stem cell homing and mobilization: review on bioactive lipids as potent chemoattractants and cationic peptides as underappreciated modulators of responsiveness to SDF-1 gradients

Leukemia volume 26, pages 63–72 (2012)Cite this article

Abstract

Hematopoietic stem progenitor cells (HSPCs) respond robustly to α-chemokine stromal-derived factor-1 (SDF-1) gradients, and blockage of CXCR4, a seven-transmembrane-spanning GαI-protein-coupled SDF-1 receptor, mobilizes HSPCs into peripheral blood. Although the SDF-1–CXCR4 axis has an unquestionably important role in the retention of HSPCs in bone marrow (BM), new evidence shows that, in addition to SDF-1, the migration of HSPCs is directed by gradients of the bioactive lipids sphingosine-1 phosphate and ceramide-1 phosphate. Furthermore, the SDF-1 gradient may be positively primed/modulated by cationic peptides (C3a anaphylatoxin and cathelicidin) and, as previously demonstrated, HSPCs respond robustly even to very low SDF-1 gradients in the presence of priming factors. In this review, we discuss the role of bioactive lipids in stem cell trafficking and the consequences of HSPC priming by cationic peptides. Together, these phenomena support a picture in which the SDF-1–CXCR4 axis modulates homing, BM retention and mobilization of HSPCs in a more complex way than previously envisioned.

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Acknowledgements

This work was supported by NIH R01 DK074720, EU structural funds, KBN Grant (N N401 024536), Innovative Economy Operational Program POIG.01.01.02-00-109/09-01 and the Henry M and Stella M Hoenig Endowment (to MZR).

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Authors and Affiliations

  1. Stem Cell Institute, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA

    M Z Ratajczak, C H Kim, G Schneider, M Kucia & J Ratajczak

  2. Department of Physiology, Pomeranian Medical University, Szczecin, Poland

    M Z Ratajczak, M Kucia & J Ratajczak

  3. Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, Lexington, KY, USA

    A Abdel-Latif & A J Morris

  4. Hematopoietic Stem Cell Transplant Program, University of Virginia, Charlottesville, VA, USA

    M J Laughlin

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  1. M Z Ratajczak
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  2. C H Kim
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  3. A Abdel-Latif
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  4. G Schneider
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  5. M Kucia
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  6. A J Morris
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  7. M J Laughlin
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  8. J Ratajczak
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Correspondence to M Z Ratajczak.

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Ratajczak, M., Kim, C., Abdel-Latif, A. et al. A novel perspective on stem cell homing and mobilization: review on bioactive lipids as potent chemoattractants and cationic peptides as underappreciated modulators of responsiveness to SDF-1 gradients. Leukemia 26, 63–72 (2012). https://doi.org/10.1038/leu.2011.242

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  • DOI: https://doi.org/10.1038/leu.2011.242

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