Norepinephrine reuptake inhibition promotes mobilization in mice: Potential impact to rescue low stem cell yields

Daniel Lucas, Ingmar Bruns, Michela Battista, Simon Mendez-Ferrer, Claire Magnon, Yuya Kunisaki, Paul S. Frenette

研究成果: ジャーナルへの寄稿学術誌査読

78 被引用数 (Scopus)

抄録

The mechanisms mediating hematopoietic stem and progenitor cell (HSPC) mobilization by G-CSF are complex. We have found previously that G-CSF-enforced mobilization is controlled by peripheral sympathetic nerves via norepinephrine (NE) signaling. In the present study, we show that G-CSF likely alters sympathetic tone directly and that methods to increase adrenergic activity in the BM microenvironment enhance progenitor mobilization. Peripheral sympathetic nerve neurons express the G-CSF receptor and ex vivo stimulation of peripheral sympathetic nerve neurons with G-CSF reduced NE reuptake significantly, suggesting that G-CSF potentiates the sympathetic tone by increasing NE availability. Based on these data, we investigated the NE reuptake inhibitor desipramine in HSPC mobilization. Whereas desipramine did not by itself elicit circulating HSPCs, it increased G-CSF-triggered mobilization efficiency significantly and rescued mobilization in a model mimicking "poor mobilizers." Therefore, these data suggest that blockade of NE reuptake may be a novel therapeutic target to increase stem cell yield in patients.

本文言語英語
ページ(範囲)3962-3965
ページ数4
ジャーナルBlood
119
17
DOI
出版ステータス出版済み - 4月 19 2012
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 生化学
  • 免疫学
  • 血液学
  • 細胞生物学

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