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Signals from the Sympathetic Nervous
System Regulate Hematopoietic Stem Cell Egress from Bone Marrow
Yoshio Katayama1,2,5,
Michela Battista1,5, Wei-Ming Kao1,5,
Andrés Hidalgo1, Anna J. Peired1,
Steven A. Thomas4 and Paul S. Frenette1,3
1Department of Medicine,
Immunobiology Center and Black Family Stem Cell Institute, Mount Sinai
School of Medicine, New York, NY 10029, USA. 2Department of
Hematology, Oncology, and Respiratory Medicine, Okayama University
Hospital, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. 3Mount
Sinai School of Medicine, Department of Medicine, One Gustave L. Levy
Place, Box 1079, New York, NY 10029, USA. 4Department of
Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA.
5 These authors contributed equally to this work.
Correspondence to: Paul S. Frenette. E-mail: paul.frenette@mssm.edu.
Ph: 212-659-9693; Fax: 212-849-2574. Received 15 April 2005;
revised 19 September 2005; accepted 27 October 2005.
Published: January 26, 2006. Available online 26 January 2006.
Hematopoietic stem and progenitor cells
(HSPC), attracted by the chemokine CXCL12, reside in specific niches
in the bone marrow (BM).
HSPC migration out of the BM is a critical process that underlies
modern clinical stem cell transplantation.
Here we demonstrate that enforced HSPC egress from BM niches depends
critically on the nervous system.
UDP-galactose ceramide galactosyltransferase-deficient (Cgt−/−)
mice exhibit aberrant nerve conduction and display virtually no HSPC
egress from BM following granulocyte colony-stimulating factor (G-CSF)
or fucoidan administration.
Adrenergic tone, osteoblast function, and bone CXCL12 are dysregulated
in Cgt−/− mice.
Pharmacological or genetic ablation of adrenergic neurotransmission
indicates that norepinephrine (NE) signaling controls G-CSF-induced
osteoblast suppression, bone CXCL12 downregulation, and HSPC
mobilization.
Further, administration of a β2 adrenergic agonist
enhances mobilization in both control and NE-deficient mice.
Thus, these results indicate that the sympathetic nervous system
regulates the attraction of stem cells to their niche.
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