|
ИСТИНА |
Войти в систему Регистрация |
ИПМех РАН |
||
Neuroprotective properties Mesenchymal Stromal Cell-Derived Extracellular Vesicles in models acute brain pathologyстатья Исследовательская статья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или ScopusДата последнего поиска статьи во внешних источниках: 29 сентября 2021 г.
- Авторы: Golovicheva V., Danilina T., Schevchova J., Goryunov K., Gulyaev M., Plotnikov E., Zinchenko V., Zorov D., Silachev D.
- Журнал: European Journal of Clinical Investigation
- Том: 51
- Год издания: 2021
- Издательство: Blackwell Publishing Inc.
- Местоположение издательства: United Kingdom
- Первая страница: 120
- Последняя страница: 120
- Номер статьи: e13567
- DOI: 10.1111/eci.13567
- Аннотация: 55ASM-0129 FT. Introduction. In the last few years, the attention of the scientific community is focused on the study of neuroprotective properties of extracellular vesicles (EV) derived from multipotent mesenchymal stromal cells (MSC). However, the molecular mechanism of EV’s neuroprotective activity is not well understood.Materials and Methods. EVs were obtained from human postnatal placenta MSCs condition medium. EVs were characterized as recommended by MISEV 2018. Neuroprotective activity of EVs was evaluated using adult rat traumatic brain injury (TBI, n=30) and neonatal hypoxia-ischemia (HI, n=30) models. Neurological deficits were assessed in the Cylinder and Limb-placing tests. The volume of injury was assessed by MR imaging. The neuroprotective mechanisms of EVs were also estimated by the oxygen-glucose deprivation (OGD, 40 min) and the NH4Cl-toxicity (48 h, 8 mM) models using rat hippocampal neuroglial cells. Cells were preincubated for 24h with different concentrations of EVs. The experiments evaluated the effect of EVs on Ca2+ signaling of neurons and astrocytes before damage and during 40 min of OGD. The effect of EVs on cell survival in culture before modeling damaging conditions also was evaluated.Results. The neurological deficits assessed in the Limb Placing test significantly reduced after TBI and after induction of HI in the groups with intranasal instillation of EVs compared to the control. Analysis of the frequency of contralateral paw usage, when injured hemisphere in the "Cylinder" test, showed a significant functional recovery in the limb use in the groups with intranasal instillation of EV after TBI and HI (p = .018 and p = .015, respectively). The volume of brain damage significantly decreased in the groups with EVs treatment after TBI (from 91.5 to 64.5 mm3; p = .009) and after HI (from 1089 to 593 mm3; p = .0036). EVs significantly protected cells from death after OGD induction through a decrease in [Ca2+]i during the second phase of global cytosolic calcium influx. EVs induced aberrant [Ca2+]i oscillation in astrocytes. Incubation of hippocampal culture treated by EVs for 24 h led to a statistically significant decrease in the number of dead cells after 48 hours modeling of hyperammonemia. EVs significantly accelerated neurite growth during the development of the hippocampal neuroglial network.Conclusions. EVs demonstrate sustained neuroprotective properties in the models of TBI and neonatal HI. The therapeutic properties of EVs may be explained by their influence on the calcium signaling in neurons and astrocytes leading to the enhancement of neuroplasticity through neurite growth and development.
- Добавил в систему: Силачёв Денис Николаевич