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

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)695-703
Number of pages9
JournalNature medicine
Volume19
Issue number6
DOIs
Publication statusPublished - Jun 1 2013
Externally publishedYes

Fingerprint

Chemotherapy
Regeneration
Bone
Bone Marrow
Drug Therapy
Wounds and Injuries
Adrenergic Agents
Stem Cell Niche
Recovery
Genetic Models
Nerve Growth Factors
Stromal Cells
Hematopoietic Stem Cells
Stem cells
Neuroglia
Shielding
Cisplatin
Neurons
Pharmacology
Tissue

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Lucas, D., Scheiermann, C., Chow, A., Kunisaki, Y., Bruns, I., Barrick, C., ... Frenette, P. S. (2013). Chemotherapy-induced bone marrow nerve injury impairs hematopoietic regeneration. Nature medicine, 19(6), 695-703. https://doi.org/10.1038/nm.3155

Chemotherapy-induced bone marrow nerve injury impairs hematopoietic regeneration. / Lucas, Daniel; Scheiermann, Christoph; Chow, Andrew; Kunisaki, Yuya; Bruns, Ingmar; Barrick, Colleen; Tessarollo, Lino; Frenette, Paul S.

In: Nature medicine, Vol. 19, No. 6, 01.06.2013, p. 695-703.

Research output: Contribution to journalArticle

Lucas, D, Scheiermann, C, Chow, A, Kunisaki, Y, Bruns, I, Barrick, C, Tessarollo, L & Frenette, PS 2013, 'Chemotherapy-induced bone marrow nerve injury impairs hematopoietic regeneration', Nature medicine, vol. 19, no. 6, pp. 695-703. https://doi.org/10.1038/nm.3155
Lucas, Daniel ; Scheiermann, Christoph ; Chow, Andrew ; Kunisaki, Yuya ; Bruns, Ingmar ; Barrick, Colleen ; Tessarollo, Lino ; Frenette, Paul S. / Chemotherapy-induced bone marrow nerve injury impairs hematopoietic regeneration. In: Nature medicine. 2013 ; Vol. 19, No. 6. pp. 695-703.
@article{7a611b237fe2476fa75c7129166f3f8a,
title = "Chemotherapy-induced bone marrow nerve injury impairs hematopoietic regeneration",
abstract = "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.",
author = "Daniel Lucas and Christoph Scheiermann and Andrew Chow and Yuya Kunisaki and Ingmar Bruns and Colleen Barrick and Lino Tessarollo and Frenette, {Paul S.}",
year = "2013",
month = "6",
day = "1",
doi = "10.1038/nm.3155",
language = "English",
volume = "19",
pages = "695--703",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Chemotherapy-induced bone marrow nerve injury impairs hematopoietic regeneration

AU - Lucas, Daniel

AU - Scheiermann, Christoph

AU - Chow, Andrew

AU - Kunisaki, Yuya

AU - Bruns, Ingmar

AU - Barrick, Colleen

AU - Tessarollo, Lino

AU - Frenette, Paul S.

PY - 2013/6/1

Y1 - 2013/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84880301799&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880301799&partnerID=8YFLogxK

U2 - 10.1038/nm.3155

DO - 10.1038/nm.3155

M3 - Article

VL - 19

SP - 695

EP - 703

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

IS - 6

ER -