Temporal profile of molecular signatures associated with circulating endothelial progenitor cells in human ischemic stroke.

Department of Neurology, Clinical Neurosciences Research Laboratory, Hospital Clínico Universitario, IDIS, University of Santiago de Compostela, Santiago de Compostela, Spain.
Journal of Neuroscience Research (Impact Factor: 2.73). 04/2012; 90(9):1788-93. DOI: 10.1002/jnr.23068
Source: PubMed

ABSTRACT Endothelial progenitor cells (EPC) have been associated with good functional outcome in ischemic stroke. From preclinical studies, it has been reported that EPC proliferation is mediated by several molecular markers, including vascular endothelial growth factor (VEGF), stromal cell-derived factor-1α (SDF-1α), and the activity of matrix metalloproteinase-9 (MMP-9). Therefore, our aim was to study the role of these molecular factors in EPC proliferation in human ischemic stroke. Forty-eight patients with first episode of nonlacunar ischemic stroke were prospectively included in the study within 12 hr of symptom onset. EPC colonies were classified as early-outgrowth colony forming unit-endothelial cell (CFU-EC) and quantified at admission, at 24 and 72 hr, at day 7, and at 3 months. At the same time, serum levels of VEGF, SDF-1α, and active MMP-9 were measured by ELISA. The primary endpoint was EPC increment during the first week, which was defined as the difference in the number of CFU-EC between day 7 and admission. We found that VEGF (r = 0.782), SDF-1α (r = 0.828), and active MMP-9 (r = 0.740) levels at 24 hr from stroke onset showed a strong correlation with EPC increment. Similar results were found for VEGF levels at 72 hr (r = 0.839) and at day 7 (r = 0.602) as well as for active MMP-9 levels at 72 hr (r = 0.442) and at day 7 (r = 0.474). In the multivariate analyses, serum levels of VEGF at 72 hr (B: 0.074, P < 0.0001) and SDF-1α at 24 hr (B: 0.049, P = 0.008) were independent factors for EPC increment during the first week of evolution. These findings suggest that VEGF and SDF-1α may mediate EPC proliferation in human ischemic stroke.

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    Translational Proteomics. 06/2014;
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    ABSTRACT: The levels of circulating endothelial progenitor cells (EPCs) in ischemic stroke have not been studied extensively and reported results are inconsistent. We aimed to investigate the time course, the prognostic relevance, and the variables associated with EPC counts in patients with ischemic stroke at different time points. We studied prospectively 146 consecutive patients with ischemic stroke within the first 48 h from the onset of symptoms (baseline). We evaluated demographic data, classical vascular risk factors, treatment with thrombolysis and statins, stroke etiology, National Institute of Health and Stroke Scale score and outcome (favorable when Rankin scale score 0-2). Blood samples were collected at baseline, at day 7 after stroke (n = 121) and at 3 months (n = 92). The EPC were measured by flow cytometry. We included 146 patients with a mean age of 70.8 ± 12.2 years. The circulating EPC levels were higher on day 7 than at baseline or at 3 months (P = 0.045). Pretreatment with statins (odds ratio [OR] 3.11, P = 0.008) and stroke etiology (P = 0.032) were predictive of EPC counts in the baseline sample. EPC counts were not associated with stroke severity or functional outcome in all the patients. However, using multivariate analyses, a better functional outcome was found in patients with higher EPC counts in large-artery atherosclerosis and small-vessel disease etiologic subtypes. After acute ischemic stroke, circulating EPC counts peaked at day 7. Pretreatment with statins increased the levels of EPC. In patients with large-artery atherosclerosis and small-vessel disease subtypes, higher counts were related to better outcome at 3 months.
    Brain and behavior. 11/2013; 3(6):649-55.
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    ABSTRACT: Modified mesenchymal stromal cells (MSCs) display a unique mechanism of action during the repair phase of traumatic brain injury by exhibiting the ability to build a biobridge between the neurogenic niche and the site of injury. Immunohistochemistry and laser capture assay have visualized this biobridge in the area between the neurogenic subventricular zone and the injured cortex. This biobridge expresses high levels of extracellular matrix metalloproteinases (MMPs), which are initially co-localized with a stream of transplanted MSCs, but later this region contains only few to non-detectable grafts and becomes overgrown by newly recruited host cells. We have reported that long-distance migration of host cells from the neurogenic niche to the injured brain site can be attained via these transplanted stem cell-paved biobridges, which serve as a key regenerative process for the initiation of endogenous repair mechanisms. Thus, far the two major schools of discipline in stem cell repair mechanisms support the idea of “cell replacement” and the bystander effects of “trophic factor secretion.” Our novel observation of stem cell-paved biobridges as pathways for directed migration of host cells from neurogenic niche toward the injured brain site adds another mode of action underlying stem cell therapy. More in-depth investigations on graft-host interaction will likely aid translational research focused on advancing this stem cell-paved biobridge from its current place, as an equally potent repair mechanism as cell replacement and trophic factor secretion, into a new treatment strategy for traumatic brain injury and other neurological disorders.
    Frontiers in Systems Neuroscience 06/2014; 8.


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May 21, 2014