Chemotherapy-induced bone marrow nerve injury impairs hematopoietic regeneration

Daniel Lucas, Christoph Scheiermann, Andrew Chow, Yuya Kunisaki, Ingmar Bruns, Colleen Barrick, Lino Tessarollo, Paul S. Frenette

研究成果: ジャーナルへの寄稿学術誌査読

211 被引用数 (Scopus)

抄録

Anticancer chemotherapy drugs challenge hematopoietic tissues to regenerate but commonly produce long-term sequelae. Chemotherapy-induced deficits in hematopoietic stem or stromal cell function have been described, but the mechanisms mediating hematopoietic dysfunction remain unclear. Administration of multiple cycles of cisplatin chemotherapy causes substantial sensory neuropathy. Here we demonstrate that chemotherapy-induced nerve injury in the bone marrow of mice is a crucial lesion impairing hematopoietic regeneration. Using pharmacological and genetic models, we show that the selective loss of adrenergic innervation in the bone marrow alters its regeneration after genotoxic insult. Sympathetic nerves in the marrow promote the survival of constituents of the stem cell niche that initiate recovery. Neuroprotection by deletion of Trp53 in sympathetic neurons or neuroregeneration by administration of 4-methylcatechol or glial-derived neurotrophic factor (GDNF) promotes hematopoietic recovery. These results demonstrate the potential benefit of adrenergic nerve protection for shielding hematopoietic niches from injury.

本文言語英語
ページ(範囲)695-703
ページ数9
ジャーナルNature medicine
19
6
DOI
出版ステータス出版済み - 6月 2013
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 生化学、遺伝学、分子生物学一般

フィンガープリント

「Chemotherapy-induced bone marrow nerve injury impairs hematopoietic regeneration」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル