Ischemic stroke is the third cause of death in the developed countries and the main reason of severe disability. Brain ischemia leads to the production of damage-associated molecular patterns (DAMPs) by neurons and glial cells which results in astrocyte and microglia activation, pro-inflammatory cytokines and chemokines production, blood-brain barrier (BBB) disruption, infiltration of leukocytes from the peripheral blood into the infarcted area, and further exacerbation of tissue damage. However, some immune cells such as microglia or monocytes are capable to change their phenotype to anti-inflammatory, produce anti-inflammatory cytokines, and protect injured nervous tissue. In this situation, therapies, which will modulate the immune response after brain ischemia, such as transplantation of mesenchymal stem cells (MSCs) are catching interest. Many experimental studies of ischemic stroke revealed that MSCs are able to modulate immune response and act neuroprotective, through stimulation of neurogenesis, oligodendrogenesis, astrogenesis, and angiogenesis. MSCs 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 case with miR-124-enriched EVs administration is planned and probably there will be more clinical studies with EV transplantation in the near future.
Neurological disorders are becoming a growing burden as society ages, and there is a compelling need to address this spiraling problem. Stem cell‐based regenerative medicine is becoming an increasingly attractive approach to designing therapies for such disorders. The unique characteristics of mesenchymal stem cells (MSCs) make them among the most sought after cell sources. Researchers have extensively studied the modulatory properties of MSCs and their engineering, labeling, and delivery methods to the brain. The first part of this review provides an overview of studies on the application of MSCs to various neurological diseases, including stroke, traumatic brain injury, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease, Parkinson's disease, and other less frequently studied clinical entities. In the second part, stem cell delivery to the brain is focused. This fundamental but still understudied problem needs to be overcome to apply stem cells to brain diseases successfully. Here the value of cell engineering is also emphasized to facilitate MSC diapedesis, migration, and homing to brain areas affected by the disease to implement precision medicine paradigms into stem cell‐based therapies.
Mesenchymal stem cells (MSCs) are non-hematopoietic, multipotent stem cells derived from mesoderm, which can be easily isolated from many sources such as bone marrow, umbilical cord or adipose tissue. MSCs provide support for hematopoietic stem cells and have an ability to differentiate into multiple cell lines. Moreover, they have proangiogenic, protective and immunomodulatory properties. MSCs have the capacity to modulate both innate and adaptive immune responses, which accompany many diseases, by inhibiting pro-inflammatory reactions and stimulating anti-inflammatory activity. Recent findings revealed that the positive effect of MSCs is at least partly associated with the production of extracellular vesicles (EVs). EVs are small membrane structures, containing proteins, lipids and nuclei acids, which take part in intra-cellular communication. Many studies indicate that EVs contain protective and pro-regenerative properties and can modulate an immune response that is activated in various diseases such as CNS diseases, myocardial infarction, liver injury, lung diseases, ulcerative colitis or kidney injury. Thus, EVs have similar functions as their cells of origin and since they do not carry the risk of cell transplantation, such as tumor formation or small vessel blockage, they can be considered a potential therapeutic tool for cell-free therapy.
Microwave energy has been in use for many applications for more than 50 years, from communication, food processing, and wood drying to chemical reactions and medical therapy. The areas, where microwave technology is applied, include drying, calcination, decomposition, powder synthesis, sintering, and chemical process control. Before the year 2000, microwaves were used to produce ceramics, semiconductors, polymers, and inorganic materials; in next years, some new attempts were made as well. Nowadays, it has been found that microwave sintering can also be applied to sintered powder and ceramics and is more effective than conventional sintering. Particularly interesting is its use for the synthesis of nanomaterials. This review identifies the main sources of microwave generation, the delivery mechanisms of microwave energy, and the typical designs and configurations of microwave devices, as well as the measurement and construction material problems related to microwave technology. We focus our attention on the configurations, materials, optimized geometries, and solvents used for microwave devices, providing examples of products, especially nanoparticles and other nanomaterials. The identified microwave devices are divided into four groups, depending on the scale, the maximum pressure developed, the highest temperature for sintering, or other special multi-functions. The challenges of using microwave energy for the synthesis of nanopowders have been identified as well. The desirable characteristics of microwave reactors in the synthesis of nanostructures, as well as their superiority over conventional synthetic methods, have been presented. We have also provided a review of the commercial and self-designed microwave reactors, digestors, and sintering furnaces for technology for synthesis of nanomaterials and other industries.
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