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- W2301401394 abstract "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 α 9 β 1 /α 4 β 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 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 α 9 β 1 /α 4 β 1 within the endosteal niche. These results support using dual α 9 β 1 /α 4 β 1 inhibitors as effective, rapid and transient mobilization agents with promising clinical applications." @default.
- W2301401394 created "2016-06-24" @default.
- W2301401394 creator A5007605785 @default.
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- W2301401394 date "2016-03-15" @default.
- W2301401394 modified "2023-10-11" @default.
- W2301401394 title "Therapeutic targeting and rapid mobilization of endosteal HSC using a small molecule integrin antagonist" @default.
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- W2301401394 doi "https://doi.org/10.1038/ncomms11007" @default.
- W2301401394 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4796355" @default.
- W2301401394 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26975966" @default.
- W2301401394 hasPublicationYear "2016" @default.
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