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Novel view on hematopoietic stem cell mobilization and homing

Leukemia Supplements volume 3, pages S19–S20 (2014)Cite this article

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We also noticed that in contrast to BM-residing HSPCs, HSPCs already circulating in PB are desensitized in their responsiveness to S1P.6, 7 Thus, this supports further that a major homing factor for HSPCs is SDF-1. We also demonstrated that the SDF-1 chemotactic gradient may be positively primed/enhanced by some cationic peptide (C3a anaphylatoxin, LL-37 cathelicidin and α2-defensin) members of the innate immunity network and HSPCs respond robustly, even to very low SDF-1 gradients in the presence of these priming factors.6, 7 All these cationic peptides are upregulated in BM microenvironment conditioned by radio/chemotherapy for transplantation. Therefore, this phenomenon has an important role in homing of HSPCs from PB into BM and, as I postulate, could be implemented in hematopoietic transplants to ex vivo prime/enhance responsiveness HSPCs to be transplanted to SDF-1 gradient present in BM.4

The role of SDF-1 gradient in homing of HSPCs could be also supported by several other HSPC chemoattractants including bioactive lipids (S1P, C1P and PGE2) and extracellular nucleotides (ATP and UTP).6, 7, 8 This explains, for example, why CXCR4−/− fetal liver HSPCs may home to BM in an SDF-1-independent manner9 as well as why homing of murine HSPCs made refractory to SDF-1 by incubation and co-injection with a CXCR4 receptor antagonist is normal or only mildly reduced.10

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Acknowledgements

MR received grant support from NIH Research Project Grant Program (R01 – DK074720 and HL112788). The symposium and publication of this supplement were sponsored by the Division of Hematology/Oncology at the Warren Alpert Medical School of Brown University and NIH Center of Biomedical Research Excellence (COBRE) for Stem Cells Biology at Rhode Island Hospital.

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

    M Z Ratajczak

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Ratajczak, M. Novel view on hematopoietic stem cell mobilization and homing. Leukemia Suppl 3 (Suppl 1), S19–S20 (2014). https://doi.org/10.1038/leusup.2014.11

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