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dc.contributor.authorCao, B
dc.contributor.authorZhang, Z
dc.contributor.authorGrassinger, J
dc.contributor.authorWilliams, B
dc.contributor.authorHeazlewood, CK
dc.contributor.authorChurches, QI
dc.contributor.authorJames, SA
dc.contributor.authorLi, S
dc.contributor.authorPapayannopoulou, T
dc.contributor.authorNilsson, SK
dc.date.accessioned2021-02-04T00:50:50Z
dc.date.available2021-02-04T00:50:50Z
dc.date.issued2016-03-01
dc.identifierpii: ncomms11007
dc.identifier.citationCao, B., Zhang, Z., Grassinger, J., Williams, B., Heazlewood, C. K., Churches, Q. I., James, S. A., Li, S., Papayannopoulou, T. & Nilsson, S. K. (2016). Therapeutic targeting and rapid mobilization of endosteal HSC using a small molecule integrin antagonist. NATURE COMMUNICATIONS, 7 (1), https://doi.org/10.1038/ncomms11007.
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/11343/259207
dc.description.abstractThe inherent disadvantages of using granulocyte colony-stimulating factor (G-CSF) for hematopoietic stem cell (HSC) mobilization have driven efforts to identify alternate strategies based on single doses of small molecules. Here, we show targeting α9β1/α4β1 integrins with a single dose of a small molecule antagonist (BOP (N-(benzenesulfonyl)-L-prolyl-L-O-(1-pyrrolidinylcarbonyl)tyrosine)) rapidly mobilizes long-term multi-lineage reconstituting HSC. Synergistic engraftment augmentation is observed when BOP is co-administered with AMD3100. Impressively, HSC in equal volumes of peripheral blood (PB) mobilized with this combination effectively out-competes PB mobilized with G-CSF. The enhanced mobilization observed using BOP and AMD3100 is recapitulated in a humanized NODSCIDIL2Rγ(-/-) model, demonstrated by a significant increase in PB CD34(+) cells. Using a related fluorescent analogue of BOP (R-BC154), we show that this class of antagonists preferentially bind human and mouse HSC and progenitors via endogenously primed/activated α9β1/α4β1 within the endosteal niche. These results support using dual α9β1/α4β1 inhibitors as effective, rapid and transient mobilization agents with promising clinical applications.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleTherapeutic targeting and rapid mobilization of endosteal HSC using a small molecule integrin antagonist
dc.typeJournal Article
dc.identifier.doi10.1038/ncomms11007
melbourne.affiliation.departmentClinical Pathology
melbourne.affiliation.departmentFlorey Department of Neuroscience and Mental Health
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleNature Communications
melbourne.source.volume7
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1207482
melbourne.contributor.authorJames, Simon
melbourne.contributor.authorNilsson, Susan
dc.identifier.eissn2041-1723
melbourne.accessrightsOpen Access


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