br Introduction Cerebral stroke causes an efflux
Introduction Cerebral stroke causes an efflux of various groups of progenitor and stem cells from bone marrow to bloodstream and the levels of these cells correlate with neurological status of stroke patients (Gójska-Grymajło et al., 2012, 2018). It is thought that paracrine factors produced by the injured cerebral tissue attract progenitor/stem cells that in turn secrete a variety of trophic factors and extracellular vesicles that help to restore function of the ischemic region and enhance neuroplasticity (Beer et al., 2016). There are numerous reports on trials with the use of various stem cells to treat ischemic stroke patients. However, the optimal route, the amount of cells, and the time of administration remain unknown (Bang et al., 2016; Muir, 2017). In our recent study we have hypothesized that tracing down the subgroups of progenitor/stem cells specifically evoked from bone marrow by Nilvadipine structure ischemia could result in finding the optimal subgroup of cells to be used in cell or secretome therapies (Gójska-Grymajło et al., 2018). Neuron specific enolase (NSE) is an isoenzyme of the glycolytic enzyme enolase, found in the cytoplasm of neurons and cells of neuroendocrine origin. It is measurable in blood and cerebrospinal fluid. NSE can bind plasminogen on the cell surface and promote pericellular plasminogen activation, extracellular matrix (ECM) degradation, proliferation of inflammatory glial cells and invasion and metastasis of tumor cells (Haque et al., 2016; Lamers et al., 1995). It has been proved that NSE levels rise after ischemic and haemorrhagic stroke, and subarachnoidal bleeding. Initially, NSE together with S100b, were expected to be good early prognostic markers for acute ischemic stroke (Oh et al., 2003; Wunderlich et al., 2004, 1999). However, following the release of some conflicting data, NSE is eventually thought to have low predictive power in the early hours after the ischemic insult, but the more delayed the sampling, the greater the correlation with stroke clinical characteristics (Ahmad et al., 2012; Anand and Stead, 2005; Fanucchi et al., 2000; González-García et al., 2012; Tomasiuk and Friedman, 2010). Similarly to our previous study (Gójska-Grymajło et al., 2018), we have chosen the following progenitor/stem cells: CD45−CD34 + CD271+ (mesenchymal progenitor cells), CD45− CD34 + CXCR4+ and CD45−CD34 + CXCR7+ progenitor/stem cells (cells mobilized into the peripheral blood through SDF1α-CXCR4+/CXCR7+ axis) and CD45−CD34 + CD133+ (endothelial progenitor cells). CD133 + endothelial progenitor cells have been most thoroughly studied in ischemic stroke and are suspected of the high regenerative potential (Bakondi et al., 2009). CXCR4 and CXCR7 receptors determine the migration of cells towards the ischemic lesion along SDF-1α–CXCR4/CXCR7 axis. Progenitor/stem cells with CXCR4 receptor were the object of our first study, which showed that their levels and dynamics seem to correlate with clinical parameters of stroke patients (Gójska-Grymajło et al., 2012). In the next study, we were the first to report on CXCR7+ stem cells in the peripheral blood of stroke patients, with results suggesting separate function of the CXCR7 receptor (Gójska-Grymajło et al., 2018). We were also the first to report on the CD271 + stem cells which are mesenchymal progenitor cells with high proliferative and multipotential differentiation ability, found in adult bone marrow and adipose tissue and that had been earlier proved to be mobilized early after myocardial infarction (Quirici et al., 2010; Iso et al., 2012; Gójska-Grymajło et al., 2018).
Materials and methods
Discussion In terms of MFI levels, only the CD45−CD34 + CXCR7+ cells significantly and negatively correlated with NSE concentrations. This finding seems especially interesting in the light of the results of our recent study and the newest reports of other research groups, which seem to indicate the separate or even dominating function of the SDF-1 –CXCR7 over SDF-1 - CXCR4 axis in acute ischemic stroke. In our recent study we have found that stroke patients had lower levels of the CD45−CD34 + CXCR7+ cells than subjects from the control group and patients who received the thrombolytic treatment had higher levels of these cells in comparison with the ones without the treatment. We have not found such differences for the CD45 + CD34 + CXCR4+ cells (Gójska-Grymajło et al., 2018). It has been recently reported that protein expression of SDF-1 and CXCR7, but not CXCR4, were significantly increased in the cortical peri-infarct regions (penumbra) after ischemic stroke in human, compared with adjacent normal tissues and control subjects (Zhang et al., 2018). Additionally, in a study of cerebral ischemia/reperfusion rat hippcampus model, overexpression of CXCR7 promoted migration of mesenchymal stem cells toward an SDF-1 gradient, and the effect of CXCR7 was stronger than that of CXCR4 (Wang et al., 2014). Since myocardial infarction (MI) shares some of the pathophysiological aspects with cerebral stroke, it is worth mentioning that in a study on coronary arteries of mice and humans, CXCR7 turned out to promote endothelial proliferation and angiogenesis after MI and CXCR7 gene delivery via left ventricular injection and treatment with a CXCR7 agonist offered cardiac protection after MI (Hao et al., 2017).