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Neurological Regulation of the Bone Marrow Niche

  • Fatima Aerts-KayaEmail author
  • Baris Ulum
  • Aynura Mammadova
  • Sevil Köse
  • Gözde Aydin
  • Petek Korkusuz
  • Duygu Uçkan-Çetinkaya
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1212)

Abstract

The bone marrow (BM) hematopoietic niche is the microenvironment where in the adult hematopoietic stem and progenitor cells (HSPCs) are maintained and regulated. This regulation is tightly controlled through direct cell-cell interactions with mesenchymal stromal stem (MSCs) and reticular cells, adipocytes, osteoblasts and endothelial cells, through binding to extracellular matrix molecules and through signaling by cytokines and hematopoietic growth factors. These interactions provide a healthy environment and secure the maintenance of the HSPC pool, their proliferation, differentiation and migration. Recent studies have shown that innervation of the BM and interactions with the peripheral sympathetic neural system are important for maintenance of the hematopoietic niche, through direct interactions with HSCPs or via interactions with other cells of the HSPC microenvironment. Signaling through adrenergic receptors (ARs), opioid receptors (ORs), endocannabinoid receptors (CRs) on HSPCs and MSCs has been shown to play an important role in HSPC homeostasis and mobilization. In addition, a wide range of neuropeptides and neurotransmitters, such as Neuropeptide Y (NPY), Substance P (SP) and Tachykinins, as well as neurotrophins and neuropoietic growth factors have been shown to be involved in regulation of the hematopoietic niche. Here, a comprehensive overview is given of their role and interactions with important cells in the hematopoietic niche, including HSPCs and MSCs, and their effect on HSPC maintenance, regulation and mobilization.

Keywords

Bone Marrow Niche Endocannabinoids Hematopoiesis Neuropeptides Opioids Tachykinins 

Abbreviations

2-AG

2-ArachidonoylGlycerol

ACh

acetylcholine

AEA

Anandamide

AGM

aorta-gonad-mesonephros

ARs

adrenergic receptors

BDNF

Brain-Derived Growth factor

BM

bone marrow

CBD

Cannabidiol

CD271

Low affinity nerve growth factor receptor

CFU-F

Colony Forming Unit-Fibroblast

CFU-GEMM

Colony Forming Unit-Granulocyte/Erythrocyte/Monocyte/Megakaryocyte

ChAT

choline acetyltransferase

CKs

cytokines

CNS

central nervous system

CNTF

ciliary neurotrophic factor

CRs

endocannabinoid receptors

CT-1

cardiotrophin-1

CXCL12/SDF1

Stromal Derived Factor-1

D

Dopamine

DCs

Dendritic cells

DRs

dopamine receptors

E

Epinephrine/Adrenaline

ECB

Endocannabinoid

ECM

extracellular matrix

ECs

endothelial cells

EK

Endokinin

FAAH

fatty acid amide hydrolase

FGF

Fibroblasts growth factor

FTOC

fetal thymus organ cultures

G-CSF

Granulocyte-Colony Stimulating Factor

GDNF

glial cell-line derived neurotrophic factor

GDNF

Glial-derived Neurotrophic Factor

GFLs

GDNF family of ligands

GM-CSF

Granulocyte/Macrophage-Colony Stimulating Factor

GPCRs

G-protein coupled receptors

HGFs

hematopoietic growth factors

HK-1

Hemokinin-1

HSCs

hematopoietic stem cells

HSPCs

hematopoietic stem and progenitor cells

IL

Interleukin

LIF

Leukemia inhibiting factor

LSK cells

LinSca+c-kit+ cells

MIP1α

Macrophage Inflammatory Protein-1alpha

MMP

Metalloproteinase

MSCs

mesenchymal stromal/stem cells

NE

Norepinephrine/Noradrenaline

NGF

Nerve growth factor

NK cell

Natural Killer cell

NKA

Neurokinin A

NKB

Neurokinin B

NK-Rs

Neurokinin receptors

NPY

Neuropeptide Y

NTs

Neurotrophins

OBs

osteoblasts

ORs

opioid receptors

OSM

Oncostatin M

PAA

periarterial adventitial cells

PDGF

Platelet-derived growth factor

RET

rearranged during transfection receptor

RTK

receptor tyrosine kinase

SCF

Stem Cell Factor

SNS

sympathetic nervous system

SP

Substance P

TGFβ

Transforming Growth Factor

TH

tyrosine hydrolase

THC

Tetrahydrocannabinol

TK

Tachykinins

TLRs

Toll-like receptors

TNFR

Tumor necrosis factor receptor

TNFα

Tumor Necrosis Factor alpha

TPO

Thrombopoietin

Trk

tropomyosin receptor kinase

UCB

Umbilical Cord Blood

VEGF

Vascular endothelial growth factor

WT

Wild type

Notes

Acknowledgements

This manuscript was supported by grants from the Scientific and Technological Research Council of Turkey, project no 318S073 and the Hacettepe University, Scientific Research Project Coordination Unit TYL-2018-17435 and THD-2018-17209.

Conflicts of Interest

The authors declare no conflict of interest.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Fatima Aerts-Kaya
    • 1
    • 2
    Email author
  • Baris Ulum
    • 2
    • 3
  • Aynura Mammadova
    • 1
    • 2
  • Sevil Köse
    • 4
  • Gözde Aydin
    • 1
    • 2
  • Petek Korkusuz
    • 1
    • 5
  • Duygu Uçkan-Çetinkaya
    • 1
    • 2
  1. 1.Graduate School of Health Sciences, Department of Stem Cell SciencesHacettepe UniversityAnkaraTurkey
  2. 2.Center for Stem Cell Research and DevelopmentHacettepe UniversityAnkaraTurkey
  3. 3.Faculty of Arts and Sciences, Department of Biological SciencesMiddle East Technical UniversityAnkaraTurkey
  4. 4.Faculty of Health Sciences, Department of Medical BiologyAtilim UniversityAnkaraTurkey
  5. 5.Faculty of Medicine, Department of Histology and EmbryologyHacettepe UniversityAnkaraTurkey

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