Revascularization and endothelial progenitor cells in stroke

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Stroke is one of the leading causes of death and disability worldwide. Tremendous improvements have been achieved in the acute care of stroke patients with the implementation of stroke units, thrombolytic drugs, and endovascular trombectomies. However, stroke survivors with neurological deficits require long periods of neurorehabilitation, which is the only approved therapy for poststroke recovery. With this scenario, more treatments are urgently needed, and only the understanding of the mechanisms of brain recovery might contribute to identify new therapeutic agents. Fortunately, brain injury after stroke is counteracted by the birth and migration of several populations of progenitor cells towards the injured areas, where angiogenesis and vascular remodeling play a key role providing trophic support and guidance during neurorepair. Endothelial progenitor cells (EPCs) constitute a pool of circulating bone-marrow derived cells that mobilize after an ischemic injury with the potential to incorporate into the damaged endothelium, to form new vessels, or to secrete trophic factors stimulating vessel remodeling. The circulating levels of EPCs are altered after stroke, and several subpopulations have proved to boost brain neurorepair in preclinical models of cerebral ischemia. The goal of this review is to discuss the current state of the neuroreparative actions of EPCs, focusing on their paracrine signaling mechanisms thorough their secretome and released extracellular vesicles.

Related collections

Most cited references 119

Record: found
Abstract: found
Article: not found

Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.

Hadi Valadi, Karin Ekström, Apostolos Bossios … (2007)

Exosomes are vesicles of endocytic origin released by many cells. These vesicles can mediate communication between cells, facilitating processes such as antigen presentation. Here, we show that exosomes from a mouse and a human mast cell line (MC/9 and HMC-1, respectively), as well as primary bone marrow-derived mouse mast cells, contain RNA. Microarray assessments revealed the presence of mRNA from approximately 1300 genes, many of which are not present in the cytoplasm of the donor cell. In vitro translation proved that the exosome mRNAs were functional. Quality control RNA analysis of total RNA derived from exosomes also revealed presence of small RNAs, including microRNAs. The RNA from mast cell exosomes is transferable to other mouse and human mast cells. After transfer of mouse exosomal RNA to human mast cells, new mouse proteins were found in the recipient cells, indicating that transferred exosomal mRNA can be translated after entering another cell. In summary, we show that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location. We propose that this RNA is called "exosomal shuttle RNA" (esRNA).

0 comments Cited 2298 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

A randomized trial of intraarterial treatment for acute ischemic stroke.

Olvert Berkhemer, Puck Fransen, Debbie Beumer … (2015)

In patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion, intraarterial treatment is highly effective for emergency revascularization. However, proof of a beneficial effect on functional outcome is lacking. We randomly assigned eligible patients to either intraarterial treatment plus usual care or usual care alone. Eligible patients had a proximal arterial occlusion in the anterior cerebral circulation that was confirmed on vessel imaging and that could be treated intraarterially within 6 hours after symptom onset. The primary outcome was the modified Rankin scale score at 90 days; this categorical scale measures functional outcome, with scores ranging from 0 (no symptoms) to 6 (death). The treatment effect was estimated with ordinal logistic regression as a common odds ratio, adjusted for prespecified prognostic factors. The adjusted common odds ratio measured the likelihood that intraarterial treatment would lead to lower modified Rankin scores, as compared with usual care alone (shift analysis). We enrolled 500 patients at 16 medical centers in The Netherlands (233 assigned to intraarterial treatment and 267 to usual care alone). The mean age was 65 years (range, 23 to 96), and 445 patients (89.0%) were treated with intravenous alteplase before randomization. Retrievable stents were used in 190 of the 233 patients (81.5%) assigned to intraarterial treatment. The adjusted common odds ratio was 1.67 (95% confidence interval [CI], 1.21 to 2.30). There was an absolute difference of 13.5 percentage points (95% CI, 5.9 to 21.2) in the rate of functional independence (modified Rankin score, 0 to 2) in favor of the intervention (32.6% vs. 19.1%). There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage. In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intraarterial treatment administered within 6 hours after stroke onset was effective and safe. (Funded by the Dutch Heart Foundation and others; MR CLEAN Netherlands Trial Registry number, NTR1804, and Current Controlled Trials number, ISRCTN10888758.).

0 comments Cited 951 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes.

Joanna Kowal, Guillaume Arras, Marina Colombo … (2016)

Extracellular vesicles (EVs) have become the focus of rising interest because of their numerous functions in physiology and pathology. Cells release heterogeneous vesicles of different sizes and intracellular origins, including small EVs formed inside endosomal compartments (i.e., exosomes) and EVs of various sizes budding from the plasma membrane. Specific markers for the analysis and isolation of different EV populations are missing, imposing important limitations to understanding EV functions. Here, EVs from human dendritic cells were first separated by their sedimentation speed, and then either by their behavior upon upward floatation into iodixanol gradients or by immuno-isolation. Extensive quantitative proteomic analysis allowing comparison of the isolated populations showed that several classically used exosome markers, like major histocompatibility complex, flotillin, and heat-shock 70-kDa proteins, are similarly present in all EVs. We identified proteins specifically enriched in small EVs, and define a set of five protein categories displaying different relative abundance in distinct EV populations. We demonstrate the presence of exosomal and nonexosomal subpopulations within small EVs, and propose their differential separation by immuno-isolation using either CD63, CD81, or CD9. Our work thus provides guidelines to define subtypes of EVs for future functional studies.