Mobilization of CD133+ Progenitor Cells in Patients with Acute Cerebral Infarction

Sepp, Dominik; Franz, Daniela; Triftshaeuser, Natalie; Ott, Ilka; Esposito-Bauer, Lorena; Feurer, Regina; Seifert, Christian L.; Thaler, Markus; Hemmer, Bernhard; Poppert, Holger

doi:10.1371/journal.pone.0070796

Cited by 9 publications

(6 citation statements)

References 30 publications

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“…A further consequence of stroke is a dramatic change in the composition of the blood, particularly with respect to circulating growth factors and cytokines . One critically important growth factor is VEGF which rises significantly in blood after MCAO .…”

Section: Discussionmentioning

confidence: 99%

“…Although local hypoxic and tissue‐secreted factors in the niche have been widely studied as triggers for stem cell proliferation in normal and injured brains , only a few reports have shown a role for circulating factors regulating downstream stem cell responses and those do not offer an underlying pathway/mechanism . It is well established that after stroke, the levels of circulating growth factors and cytokines rise dramatically in blood . One particularly important factor is vascular endothelial growth factor (VEGF), which is associated with enhanced angiogenesis and neurogenesis in the ischemic brain .…”

Section: Introductionmentioning

confidence: 99%

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Systemic Factors Trigger Vasculature Cells to Drive Notch Signaling and Neurogenesis in Neural Stem Cells in the Adult Brain

et al. 2018

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It is well documented that adult neural stem cells (NSCs) residing in the subventricular zone (SVZ) and the subgranular zone (SGZ) are induced to proliferate and differentiate into new neurons after injury such as stroke and hypoxia. However, the role of injury-related cues in driving this process and the means by which they communicate with NSCs remains largely unknown. Recently, the coupling of neurogenesis and angiogenesis and the extensive close contact between vascular cells and other niche cells, known as the neurovascular unit (NVU), has attracted interest. Further facilitating communication between blood and NSCs is a permeable blood-brain-barrier (BBB) present in most niches, making vascular cells a potential conduit between systemic signals, such as vascular endothelial growth factor (VEGF), and NSCs in the niche, which could play an important role in regulating neurogenesis. We show that the leaky BBB in stem cell niches of the intact and stroke brain can respond to circulating VEGF 165 to drive induction of the Notch ligand DLL4 (one of the most important cues in angiogenesis) in endothelial cells (ECs), pericytes, and further induce significant proliferation and neurogenesis of stem cells. STEM CELLS 2019;37:395-406 SIGNIFICANCE STATEMENTThe leaky blood-brain barrier in niches of the intact and stroke brain can respond to circulating VEGF 165 to drive neural stem cells (NSCs) activation and neurogenesis. Vascular endothelial growth factor (VEGF 165 ) induces expression of the Notch ligand DLL4 in endothelial cells, pericytes, after stroke or oxygen-glucose deprivation. The enhanced DLL4-Notch signaling and crosstalk between vasculature cells and NSCs regulate the activities of NSCs when triggered by systemic stroke-induced factors. Animals were divided into seven different groups according to the experiments. For more details, please see Supporting Information Material and Methods.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Systemic Factors Trigger Vasculature Cells to Drive Notch Signaling and Neurogenesis in Neural Stem Cells in the Adult Brain

et al. 2018

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“…Acute CI is one of the most common diseases in clinical neurology [ 21 ]. The morbidity and mortality of acute CI are relatively high, which has become one of the main diseases endangering human health [ 22 , 23 ]. The occurrence of acute CI is due to the lack of blood supply to the brain tissue or the disorder caused by cerebral vascular flow instability and brain tissue in a long period of hypoxia, ischemia, and necrosis [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of efficacy and safety of Reteplase and Alteplase in the treatment of hyper-acute cerebral infarction

et al. 2018

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Objective: The present study aimed to investigate the efficacy and safety of Reteplase (rPA) and Alteplase (rt-PA) in the treatment of hyper-acute cerebral infarction (CI).Methods: Six hundred and eleven patients with hyper-acute CI selected from September 2014 to September 2016 were assigned into the aspirin, rt-PA, rPA, rt-PA + aspirin, and rPA + aspirin groups based on their willingness. The difference of efficacy in five groups were evaluated with National Institute of Health Stroke Scale (NIHSS), modified rankin scale (mRS), and Barthel Index (BI). Coagulation function, blood lipid, and hemodynamics were analyzed. The safety differences were compared by observing the adverse reactions.Results: Compared with the rt-PA, rPA, and aspirin groups, NIHSS score, mRS score, the incidence of non- and symptomatic cerebral hemorrhage as well as the rate of adverse reactions were decreased, while BI were increased in the rt-PA + aspirin and rPA + aspirin groups after treatment. Compared with the rt-PA and rPA groups, total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were lower, whereas the hematocrit, whole blood high shear viscosity, whole blood low shear viscosity, plasma viscosity, erythrocyte electrophoresis time, fibrinogen, erythrocyte sedimentation rate (ESR), K value in blood sedimentation equation, and the comprehensive abnormality degree of blood rheology were higher in the rt-PA + aspirin and rPA + aspirin groups.Conclusion: The efficacy and safety of rt-PA or rPA combined with aspirin in the treatment of hyper-acute CI were better than those of rPA or rt-PA monotherapy.

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“…12, 13 Acute tissue injury such as ischemia and infarction mobilizes PC into the circulation. 14–20 Lower circulating PC counts and impaired PC activity measured by colony forming and migration assays have been reported in subjects with RFs for CVD in some but not all studies. 21–23 It is also unclear in humans whether aging alters circulating PC numbers, whether exposure to the injurious effects of CVD RFs stimulates or inhibits PC, and whether presence of atherosclerotic CVD is associated with impairment of PC.…”

Section: Introductionmentioning

confidence: 97%

Age and Human Regenerative Capacity Impact of Cardiovascular Risk Factors

Mheid

Hayek

et al. 2016

Circulation Research

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Rationale We investigated aging of human endogenous reparative capacity and aimed to clarify whether it is affected by presence of cardiovascular disease or its risk factors. Objective Circulating progenitor cell (PC) levels reflect endogenous regenerative potential. The effect on PC of healthy aging compared to aging with risk factors (RF) or cardiovascular disease (CVD) is unknown. We examined whether exposure to RF and CVD leads to an accelerated decline in circulating PC with increasing age. Methods and Results In 2,792 adult subjects, 498 were free of RFs (smoking, diabetes, hypertension or hyperlipidemia); 1036 subjects had 1–2 RF, and 1253 had ≥3 RFs and/or CVD. PC were enumerated by flow cytometry as CD45med+ mononuclear cells expressing CD34 and subsets co-expressing CD133, CXCR4, and vascular endothelial growth factor receptor-2 (VEGF2R) epitopes. Younger age, male gender and larger body size correlated with higher PC counts (p<0.01). After multivariable adjustment, both age and RF categories were independently associated with PC counts (p<0.05), with lower PC counts in older subjects and those with higher RF burden or CVD. PC counts remained unchanged with increasing age in healthy individuals. There were significant interactions between age and RF categories (p≤0.005), such that for younger subjects (<40 years), RFs were associated with increased PC counts, whereas for older subjects (>60 years), RFs and CVD were associated with lower PC counts. Conclusion Circulating PC levels do not decline with healthy aging; RF exposure at a younger age stimulates PC mobilization whereas continued exposure is associated with lower PC levels in later life. Over the lifespan, exposure to RFs and CVD is associated with an initial stimulation and subsequent decline in circulating PC levels, which reflect endogenous regenerative capacity.

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Mobilization of CD133+ Progenitor Cells in Patients with Acute Cerebral Infarction

Cited by 9 publications

References 30 publications

Systemic Factors Trigger Vasculature Cells to Drive Notch Signaling and Neurogenesis in Neural Stem Cells in the Adult Brain

Systemic Factors Trigger Vasculature Cells to Drive Notch Signaling and Neurogenesis in Neural Stem Cells in the Adult Brain

Evaluation of efficacy and safety of Reteplase and Alteplase in the treatment of hyper-acute cerebral infarction

Age and Human Regenerative Capacity Impact of Cardiovascular Risk Factors

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