The Brain-Bone-Blood Triad: Traffic Lights for Stem-Cell Homing and Mobilization

Lapidot, Tsvee

doi:10.1182/asheducation-2010.1.1

Cited by 79 publications

(84 citation statements)

References 40 publications

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“…[29][30][31] To further characterize changes in S1P plasma levels during G-CSF administration, we measured its levels at several time points and found an increase as soon as 30 minutes after a single G-CSF injection with a peak at day 4 of consecutive G-CSF administrations ( Figure 3I). Interestingly, S1P/S1P 1 …”

Section: Dynamic Changes In S1p Levels In the Bm And Pb Regulate G-csmentioning

confidence: 99%

“…Sphk1 knockout (KO) mice and S1P 1 loxP/loxP conditional KO mice (both on C57BL/6 background) were kindly provided by Prof Richard L. Proia (National Institutes of Health). S1P 1 loxP/loxP conditional KO mice were crossed with Mx1-Cre mice (The Jackson Laboratory) and we used S1P 1 loxP/loxP /Mx1-Cre ϩ (S1P 1 KO) and S1P 1 loxP/loxP /Mx1-Cre Ϫ (wild-type [WT] counterparts). Mice were mobilized by G-CSF (Filgastrim, Amgen; 300 g/kg) as previously described, 24 or by AMD3100 (Sigma-Aldrich; 5 mg/kg) as previously described.…”

Section: Mice and In Vivo Protocolsmentioning

confidence: 99%

“…32 S1P stimulates distinct pathways such as Rho GTPase, phospholipase C, Ras, MAP kinase, and PI3K signaling pathways depending on the expression patterns of its receptors. 31 One of these receptors, S1P 1 , is involved in lymphocyte egress from lymphoid organs 32,33 as well as from the BM 34,35 into circulatory fluids via a gradient of S1P. Interestingly, S1P can directly act as a chemoattractant for HSPCs in a dose-dependent manner.…”

Section: Introductionmentioning

confidence: 99%

“…These cells are continuously released at basal levels from the bone marrow (BM) reservoir to the circulation during steady state homeostasis together with maturing leukocytes, and at increased rates on stress situations, such as bleeding or inflammation. 1,2 The complex process of HSPC trafficking is orchestrated by various cytokines, chemokines, proteolytic enzymes, and adhesion molecules [3][4][5] through a dynamic interplay between the immune and nervous systems within the bone microenvironment. 1,2,6-8 HSPC mobilization can be clinically induced by a variety of cytokines and drugs, such as granulocyte colony stimulating factor (G-CSF, the most commonly used agent), 9,10 sulfated polysaccharides, 11,12 and recently also by AMD3100.…”

Section: Introductionmentioning

confidence: 99%

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S1P promotes murine progenitor cell egress and mobilization via S1P1-mediated ROS signaling and SDF-1 release

Golan

Vagima

Ludin

et al. 2012

Blood

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The mechanisms of hematopoietic progenitor cell egress and clinical mobilization are not fully understood. Herein, we report that in vivo desensitization of Sphingosine-1-phosphate (S1P) receptors by FTY720 as well as disruption of S1P gradient toward the blood, reduced steady state egress of immature progenitors and primitive Sca-1 ؉ /c-Kit ؉ /Lin ؊ (SKL) cells via inhibition of SDF-1 release. Administration of AMD3100 or G-CSF to mice with deficiencies in either S1P production or its receptor S1P 1 , or pretreated with FTY720, also resulted in reduced stem and progenitor cell mobilization. Mice injected with AMD3100 or G-CSF demonstrated transient increased S1P levels in the blood mediated via mTOR signaling, as well as an elevated rate of immature c-Kit ؉ /Lin ؊ cells expressing surface S1P 1 in the bone marrow (BM). Importantly, we found that S1P induced SDF-1 secretion from BM stromal cells including Nestin ؉ mesenchymal stem cells via reactive oxygen species (ROS) signaling. Moreover, elevated ROS production by hematopoietic progenitor cells is also regulated by S1P. Our findings reveal that the S1P/S1P 1 axis regulates progenitor cell egress and mobilization via activation of ROS signaling on both hematopoietic progenitors and BM stromal cells, and SDF-1 release. The dynamic cross-talk between S1P and SDF-1 integrates BM stromal cells and hematopoeitic progenitor cell motility. (Blood. 2012;119(11):2478-2488) IntroductionMotility is a key feature of hematopoietic stem and progenitor cells (HSPCs). These cells are continuously released at basal levels from the bone marrow (BM) reservoir to the circulation during steady state homeostasis together with maturing leukocytes, and at increased rates on stress situations, such as bleeding or inflammation. 1,2 The complex process of HSPC trafficking is orchestrated by various cytokines, chemokines, proteolytic enzymes, and adhesion molecules 3-5 through a dynamic interplay between the immune and nervous systems within the bone microenvironment. 1,2,6-8 HSPC mobilization can be clinically induced by a variety of cytokines and drugs, such as granulocyte colony stimulating factor (G-CSF, the most commonly used agent), 9,10 sulfated polysaccharides, 11,12 and recently also by AMD3100. 13,14 Repetitive G-CSF administrations cause mobilization by inducing proliferation and differentiation of HSPC, thus increasing their pool size, accompanied by reduced retention in the BM microenvironment. 15 The chemokine stromal cell-derived factor-1 (SDF-1, also termed CXCL12), which is the most powerful chemoattractant of both human and murine HSPCs, 16,17 and its major receptor CXCR4 are key players in HSPC mobilization. 10,12,13,[18][19][20][21] SDF-1 is transiently increased in the murine BM during G-CSF stimulation followed by its downregulation at both protein 18,22 and mRNA 23 levels, reaching a nadir at the peak of HSPC mobilization. 18 The intensified SDF-1/CXCR4 interactions induce enhanced production of reactive oxygen species (ROS) through activation of the HGF/c-Met path...

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Section: Dynamic Changes In S1p Levels In the Bm And Pb Regulate G-csmentioning

confidence: 99%

Section: Mice and In Vivo Protocolsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

S1P promotes murine progenitor cell egress and mobilization via S1P1-mediated ROS signaling and SDF-1 release

Golan

Vagima

Ludin

et al. 2012

Blood

Self Cite

177

190

View full text Add to dashboard Cite

show abstract

“…Sympathetic signals from the nervous system activated by circadian rhythms or stress conditions control HSPC motility and development also indirectly, by way of bone remodelling processes. Osteoblastic cells are involved in HSC lodgement, self-renewal and function, while bone resorbing osteoclasts regulate bone turnover and progenitor cell detachment and release from the BM; the balance toward osteoclast activation and osteoblast suppression, in turn, is known to be regulated by signals from the nervous system, particularly beta-adrenergic signals (Kollet et al, 2012;Lapidot and Kollet, 2010). Additionally, a b2-adrenergic receptor agonist rescued the mobilization defects in mice deficient in dopamine b-hydroxylase and augmented G-CSF-induced HSPC mobilization.…”

Section: Stem Cells and Neural Signalling In Vertebratesmentioning

confidence: 99%

Stem cells and neural signalling: the case of neoblast recruitment and plasticity in low dose X-ray treated planarians

Rossi¹,

Iacopetti²,

Salvetti³

2012

Int. J. Dev. Biol.

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Planarians (Platyhelminthes) possess an abundant population of adult stem cells, the neoblasts, capable to give rise to both somatic and germ cells. Although neoblasts share similar morphological features, several pieces of evidence suggest that they constitute a heterogeneous population of cells with distinct ultrastructural and molecular features. We found that in planarians treated with low X-ray doses (5 Gy), only a few neoblasts survive. Among these cells, those located close to the nervous system activate an intense proliferation program and migrate to reconstitute the whole complex neoblast population. This phenomenon is inhibited by the substance P receptor antagonist spantide, and accompanied by the up-regulation of a number of genes implicated in neuronal signalling and plasticity, suggesting that signals of neural origin modulate neoblast proliferation and/or migration. Here, we review these findings and the literature available on the influence of the nervous system on stem cell activity, both in planarians and vertebrates, and we propose 5 Gy-treated planarians as a unique model system to study the influence of neural signalling on stem cell biology.

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Aging Effects on Cardiac Progenitor Cell Physiology

Rota

Goichberg

Anversa

et al. 2015

Comprehensive Physiology

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Cardiac aging has been confounded by the concept that the heart is a postmitotic organ characterized by a predetermined number of myocytes, which is established at birth and largely preserved throughout life until death of the organ and organism. Based on this premise, the age of cardiac cells should coincide with that of the organism; at any given time, the heart would be composed of a homogeneous population of myocytes of identical age. The discovery that stem cells reside in the heart and generate cardiac cell lineages has imposed a reconsideration of the mechanisms implicated in the manifestations of the aging myopathy. The progressive alterations of terminally differentiated myocytes, and vascular smooth muscle cells and endothelial cells may represent an epiphenomenon dictated by aging effects on cardiac progenitor cells (CPCs). Changes in the properties of CPCs with time may involve loss of self-renewing capacity, increased symmetric division with formation of daughter committed cells, partial depletion of the primitive pool, biased differentiation to the fibroblast fate, impaired ability to migrate, and forced entry into an irreversible quiescent state. Telomere shortening is a major variable of cellular senescence and organ aging, and support the notion that CPCs with critically shortened or dysfunctional telomeres contribute to myocardial aging and chronic heart failure. These defects constitute the critical variables that define the aging myopathy in humans. Importantly, a compartment of functionally competent human CPCs persists in the decompensated heart pointing to stem cell therapy as a novel form of treatment for the aging myopathy.

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The Brain-Bone-Blood Triad: Traffic Lights for Stem-Cell Homing and Mobilization

Cited by 79 publications

References 40 publications

S1P promotes murine progenitor cell egress and mobilization via S1P1-mediated ROS signaling and SDF-1 release

S1P promotes murine progenitor cell egress and mobilization via S1P1-mediated ROS signaling and SDF-1 release

Stem cells and neural signalling: the case of neoblast recruitment and plasticity in low dose X-ray treated planarians

Aging Effects on Cardiac Progenitor Cell Physiology

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