{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["7"],"submitter":["Cao B"],"pubmed_abstract":["The 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 ?9?1/?4?1 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 NODSCIDIL2R?(-/-) 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 ?9?1/?4?1 within the endosteal niche. These results support using dual ?9?1/?4?1 inhibitors as effective, rapid and transient mobilization agents with promising clinical applications."],"journal":["Nature communications"],"pagination":["11007"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4796355"],"repository":["biostudies-literature"],"pubmed_title":["Therapeutic targeting and rapid mobilization of endosteal HSC using a small molecule integrin antagonist."],"pmcid":["PMC4796355"],"pubmed_authors":["Grassinger J","Churches QI","Papayannopoulou T","Nilsson SK","Li S","Zhang Z","Heazlewood CK","James SA","Cao B","Williams B"],"additional_accession":[]},"is_claimable":false,"name":"Therapeutic targeting and rapid mobilization of endosteal HSC using a small molecule integrin antagonist.","description":"The 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 ?9?1/?4?1 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 NODSCIDIL2R?(-/-) 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 ?9?1/?4?1 within the endosteal niche. These results support using dual ?9?1/?4?1 inhibitors as effective, rapid and transient mobilization agents with promising clinical applications.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Mar","modification":"2021-02-21T02:05:59Z","creation":"2019-03-27T02:11:22Z"},"accession":"S-EPMC4796355","cross_references":{"pubmed":["26975966"],"doi":["10.1038/ncomms11007"]}}