There were no adverse effects of transplantation [169]

There were no adverse effects of transplantation [169]. may also have an ability to replace injured cells, but the release of paracrine factors directly into the environment or via extracellular vesicles (EVs) seems to play the most pronounced role. EVs are membrane structures containing proteins, lipids, and nucleic acids, and they express similar properties as the cells from which they are derived. However, EVs have lower immunogenicity, do not express the risk of vessel blockage, and have the capacity to cross the blood-brain barrier. Experimental studies of ischemic stroke showed that EVs have immunomodulatory and neuroprotective properties; therefore, they can stimulate neurogenesis and angiogenesis. Up to now, 20 clinical trials with MSC transplantation into patients after stroke were performed, from which two concerned on only hemorrhagic stroke and 13 studied only on ischemic stroke. There is no clinical trial with EV injection into patients after brain ischemia so far, but the Refametinib (RDEA-119, BAY 86-9766) case with miR-124-enriched EVs administration is planned and probably there will be more clinical studies with EV transplantation in the near future. strong class=”kwd-title” Keywords: Stroke, Ischemia, Neuro-inflammation, Mesenchymal stem cells, Extracellular vesicles Introduction Stem cell-based regenerative medicine is quickly catching attention, and there is an accumulation of data that positive effects of stem cell therapy frequently depend on their immunomodulatory properties. Stroke induces an extensive neuro-inflammatory response, which seems to be responsible for the propagation of brain damage. Therefore, there is a link between stem cells and stroke, which centers on inflammation, and it has a high potential to be exploited in both basic research and clinical setting. Brain ischemia Brain ischemia is one of the most important pathologies of the central nervous system (CNS). Ischemic stroke accounts for 87% of all stroke cases and it is the third most frequent cause of death people over 60?years Refametinib (RDEA-119, BAY 86-9766) old in developed countries and the leading cause of severe disability. It is estimated that every year, 15 million people in the world are affected by stroke, 5 million of which die and another 5 million suffer from long-term disability [1]. World statistics show that stroke affects women more often than men and is the second cause of death of females after 60?years old and represent 60% of all deaths caused by stroke [2]. According to the available data, 3C7% of all health care funds in developed countries are allocated for the treatment of people with stroke [3]. In ischemic stroke, serious damage of the nervous tissue occurs as a result of blocking the blood supply to the brain with subsequent insufficiency in the delivery of oxygen and Refametinib (RDEA-119, BAY 86-9766) nutrients [1]. The main factors increasing the incidence of ischemic stroke are hypertension, coronary heart disease, diabetes, smoking, hypercholesterolemia, transient ischemic attack, and atrial fibrillation [4]. During brain ischemia, the damage of the nervous tissue is observed in two areasischemic core in which the blood flow is lower than 10?mL/100?g/min and where the death of most cells occurs, and ischemic penumbra in which the blood flow is 10C20?mL/100?g/min, no neuronal death is observed but changes in tissue structure are visible. Oxygen and glucose deprivation in the area of the ischemic core leads to the reduction of neuronal adenosine triphosphate (ATP) production, which causes a decrease in the ionic gradient along the cell membrane and an increase in the Na+ ion level and Ca2+ in the cytoplasm. Glutamate accumulation and em N /em -methyl- em D /em -aspartate (NMDA) and -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor activation lead to a further influx of Ca2+ ions to the cells [1]. These Refametinib (RDEA-119, BAY 86-9766) processes result in the damage of cytoplasmic cell membrane, destruction of cell structures, activation of inflammatory cascade, and apoptosis and necrosis of cells [5]. In the ischemic penumbra, an increase in the level of glutamate derived from the ischemic core induces an increase in Ca2+ ions and Ca2+-dependent enzymes Rabbit polyclonal to ACPT which activates the production of apoptosis mediators such as nitric oxide, free radicals, or arachidonic acid [1]. These processes can initiate programmed cell death Refametinib (RDEA-119, BAY 86-9766) or necrosis depending on the magnitude of damage and the metabolic state of the cells. Currently, to treat patients after ischemic stroke, reperfusion therapy with thrombolytic drugs such as intravenous tissue plasminogen activator (tPA) or mechanical thrombectomy (MT) is used. Unfortunately, these therapies have many limitations, such as a narrow therapeutic window, which is up to 4.5?h from the onset of ischemic stroke in the case of tPA and up to 6C8?h in the case of MT, with only a limited number of cases benefiting from the extended time window till 24?h [6]. In addition, the tissue plasminogen activator is not effective for patients,.