Mesenchymal stem cells in the treatment of ischemic stroke

Over the past two decades, multiple preclinical studies have shown that transplantation of mesenchymal stem cells leads to a pronounced positive effect in animals with experimental stroke. Based on the promising results of preclinical studies, several clinical trials on the transplantation of mesenchymal stem cells to stroke patients have also been conducted. In this review, we present and analyze the results of completed clinical trials dedicated to the mesenchymal stem cells transplantation in patients with ischemic stroke. According to the obtained results, it can be concluded that transplantation of mesenchymal stem cells is safe and feasible from the economic and biomedical point of view. For the further implementa-tion of this promising approach into the clinical practice, randomized, placebo-controlled, multicenter clinical trials are needed with a large sample of patients and optimized cell transplantation protocols and patient inclusion criteria. In this review we also discuss possi-ble strategies to enhance the effectiveness of cell therapy with the use of mesenchymal stem cells

Аутотрансплантация Т-лимфоцитов как инструмент для антиген-специфической иммунотерапии онкологических заболеваний

Autotransplantation of immune cells to induce immunological rejection of tumors can be a useful approach in tumor treatment. Despite the low efficiency of this  approach demonstrated in the past, the active development of cell technologies and  genetic engineering has led to the significant improvement in clinical outcomes. A  great success was achieved in adoptive immunotherapy with the T-lymphocytes  specific to tumor antigens. This review describes the clinical experience in  application of various antigen-specific adoptive immunotherapy methods including  tumor-infiltrating T-lymphocytes, T-lymphocytes with redirected transgenic T-cell  and chimeric antigenrecognizing receptors. The possibilities and limitations of these  biomedical technologies are also analyzed in the article.Аутотрансплантация клеток иммунной системы с целью вызвать реакцию иммунологического отторжения опухоли может оказаться востребованным инструментом в руках врачей. Несмотря  на невысокую эффективность, продемонстрированную в прошлом, активное развитие  биомедицинских клеточных технологий и генной инженерии привело к значительному  улучшению результатов, получаемых при клинической апробации этого подхода. Наибольших  успехов удалось добиться в области адоптивной иммунотерапии с использованием Т-лимфоцитов,  специфичных к опухолевым антигенам. В данном обзоре описывается клинический опыт  применения различных вариантов антиген-специфической адоптивной иммунотерапии опухолей,  включая использование опухоль-инфильтрирующих T-лимфоцитов, T-лимфоцитов с перенаправленными трансгенными антигенраспознающими рецепторами, в том числе химерными.  В статье также анализируются возможности и ограничения этих биомедицинских технологий

Nuclear Polarization of Molecular Hydrogen Recombined on a Non-metallic Surface

The nuclear polarization of $\mathrm{H}_2$ molecules formed by recombination of nuclear polarized H atoms on the surface of a storage cell initially coated with a silicon-based polymer has been measured by using the longitudinal double-spin asymmetry in deep-inelastic positron-proton scattering. The molecules are found to have a substantial nuclear polarization, which is evidence that initially polarized atoms retain their nuclear polarization when absorbed on this type of surfac

Results from a combined test of an electromagnetic liquid argon calorimeter with a hadronic scintillating-tile calorimeter

The first combined test of an electromagnetic liquid argon accordion calorimeter and a hadronic scintillating-tile calorimeter was carried out at the CERN SPS. These devices are prototypes of the barrel calorimeter of the future ATLAS experiment at the LHC. The energy resolution of pions in the energy range from 20 to 300~GeV at an incident angle $\theta$ of about 11$^\circ$ is well-described by the expression \sigma/E = ((46.5 \pm 6.0)\%/\sqrt{E} +(1.2 \pm 0.3)\%) \oplus (3.2 \pm 0.4)~\mbox{GeV}/E. Shower profiles, shower leakage, and the angular resolution of hadronic showers were also studied

The HERMES Polarized Hydrogen and Deuterium Gas Target in the HERA Electron Storage Ring

The HERMES hydrogen and deuterium nuclear-polarized gas targets have been in use since 1996 with the polarized electron beam of HERA at DESY to study the spin structure of the nucleon. Polarized atoms from a Stern-Gerlach Atomic Beam Source are injected into a storage cell internal to the HERA electron ring. Atoms diffusing from the center of the storage cell into a side tube are analyzed to determine the atomic fraction and the atomic polarizations. The atoms have a nuclear polarization, the axis of which is defined by an external magnetic holding field. The holding field was longitudinal during 1996-2000, and was changed to transverse in 2001. The design of the target is described, the method for analyzing the target polarization is outlined, and the performance of the target in the various running periods is presented

Response of the ATLAS tile calorimeter prototype to muons

A study of high energy muons traversing the ATLAS hadron Tile calorimeter in the barrel region in the energy range between 10 and 300~GeV is presented. Both test beam experimental data and Monte Carlo simulations are given and show good agreement. The Tile calorimeter capability of detecting isolated muons over the above energy range is demonstrated. A signal to background ratio of about 10 is expected for the nominal LHC luminosity ($10^{34} cm^{-2} sec^{-1}$). The photoelectron statistics effect in the muon shape response is shown. The e/mip ratio is found to be $0.81 \pm 0.03$; the e/$\mu$ ratio is in the range 0.91 - 0.97. The energy loss of a muon in the calorimeter, dominated by the energy lost in the absorber, can be correlated to the energy loss in the active material. This correlation allows one to correct on an event by event basis the muon energy loss in the calorimeter and therefore reduce the low energy tails in the muon momentum distribution

Evaluation of Fermi Read-out of the ATLAS Tilecal Prototype

Prototypes of the \fermi{} system have been used to read out a prototype of the \atlas{} hadron calorimeter in a beam test at the CERN SPS. The \fermi{} read-out system, using a compressor and a 40 MHz sampling ADC, is compared to a standard charge integrating read-out by measuring the energy resolution of the calorimeter separately with the two systems on the same events. Signal processing techniques have been designed to optimize the treatment of \fermi{} data. The resulting energy resolution is better than the one obtained with the standard read-out

A measurement of the energy loss spectrum of 150 GeV muons in iron

The energy loss spectrum of 150 GeV muons has been measured with a prototype of the ATLAS hadron calorimeter in the H8 beam of the CERN SPS.\\ The differential probability $dP/dv$ per radiation length of a fractional energy loss $v = \Delta E_{\mu} / E_{\mu}$ has been measured in the range $v = 0.01 \div 0.95$; it is then compared with the theoretical predictions for energy losses due to bremsstrahlung and production of electron-positron pairs or of energetic knock-on electrons.\\ The integrated probability $\int_{0.01}^{0.95} (dP/dv) dv$ is $(1.610\pm0.015_{stat.}\pm0.105_{syst.})\cdot10^{-3}$ in agreement with the theoretical predictions of $1.556\cdot10^{-3}$ and $1.619\cdot10^{-3}$. %7.8.96 - start Agreement with theory is also found in two intervals of $v$ where production of electron-positron pairs and knock-on electrons dominates. In the region of bremsstrahlung dominance ($v = 0.12\div0.95$) the measured integrated probability $(1.160\pm0.040_{stat}\pm0.075_{syst})\cdot 10^{-4}$ is in agreement with the theoretical value of $1.185 \cdot 10^{-4}$, obtained using Petrukhin and Shestakov's \cite{PS} description of the bremsstrahlung process. The same result is about 3.6 standard deviations (defined as the quadratic sum of statistical and systematic errors) lower than the theoretical prediction of $1.472\cdot 10^{-4}$, obtained using Tsai's \cite{TS} description of bremsstrahlung

Терапевтическая эффективность внутриартериального введения нейральных прогениторных клеток, полученных из индуцированных плюрипотентных стволовых клеток, при остром экспериментальном ишемическом инсульте у крыс

Aim. Neural progenitor cells (NPC) are used for the development of cell therapies of neurological diseases. Their stereotaxic transplantation in the middle cerebral artery occlusion (MCAO) model imitating ischemic stroke results in symptom aleviation. However, exploration of less invasive transplantation options is essential, because stereotaxic transplantation is a complex procedure and can be applied to humans only by vital indications in a specialized neurological ward. The aim of the present study was to evaluate the efficacy of cell therapy of the experimental ischemic stroke by the intra-arterial transplantation of NPC.Materials and methods. NPC for transplantation (IPSC-NPC) were derived by two-stage differentiation of cells of a stable line of human induced pluripotent stem cells. Stroke modeling in rats was carried out by transitory 90 min endovascular MCAO by a silicon-tipped filament. NPC were transplanted 24 hours after MCAO. Repetitive magnetic resonance tomography of experimental animals was made with the Bruker BioSpin ClinScan tomograph with 7 Tl magnetic field induction. Animal survival rate and neurological deficit (using mNSS standard stroke severity scale) were evaluated at the 1st (before IPSC-NPC transplantation), 7th and 14th day after transplantation. Histological studies were carried out following standard protocols.Results. Intra-arterial transplantation of 7 × 105 IPSC-NPC in 1 ml at a constant 100 l/min rate in case of secured blood flow through the internal carotid artery did not cause brain capillary embolism, additional cytotoxic brain tissue edemas or other complications, while inducing increase of animal survival rate and enhanced revert of the neurological deficit. IPSC-NPC accumulation in brain after intra-arterial infusion was demonstrated. Some cells interacted with the capillary endothelium and probably penetrated through the blood-brain barrier.Conclusion. Therapeutic efficacy of the systemic, intra-arterial administration of NPC in ischemic stroke has been experimentally proven. A method of secure intra-arterial infusion of cell material into the internal carotid artery middle in rats has been developed and tested.Цель. Нейральные прогениторные клетки (НПК) используются при разработке технологий клеточной терапии неврологических заболеваний. Их стереотаксическое введение в мозг крыс после имитирующей ишемический инсульт операции окклюзии средней мозговой артерии (ОСМА) приводит к облегчению симптоматики. Однако стереотаксическое введение является сложной процедурой и для лечения болезней человека может быть применено только в специализированной клинике по жизненным показаниям, что делает необходимым исследование возможности менее травматичных способов трансплантации. Цель настоящей работы – исследование возможности проведения клеточной терапии экспериментального инсульта путем внутриартериального введения НПК.Материалы и методы. НПК для трансплантации (ИПСК-НПК) получали путем двухступенчатой дифференцировки клеток стабильной линии индуцированных плюрипотентных стволовых клеток человека. Моделирование инсульта у крыс производилось методом транзиторной (90 мин) эндоваскулярной ОСМА филаментом с силиконовым наконечником. Внутриартериальная трансплантация НПК выполнялась через 24 часа после ОСМА. Магнитно-резонансная томография экспериментальных животных в динамике проводилась на МР-томографе ClinScan фирмы Bruker BioSpin с индукцией магнитного поля 7 Тл. На 1 (до введения ИПСК-НПК), 7 и 14-е сутки после трансплантации оценивались выживаемость животных и неврологический дефицит с использованием стандартной шкалы оценки тяжести инсульта mNSS для грызунов. Гистологические исследования проводили, пользуясь стандартными методами.Результаты. Внутриартериальная трансплантация ИПСК-НПК в дозе 7 × 105 НПК в 1 мл с равномерной скоростью100 мкл/мин и поддержанием кровотока по внутренней сонной артерии не вызывала эмболии капилляров мозга, появления новых зон цитотоксического отека вещества головного мозга или других осложнений и приводила к достоверному повышению выживаемости животных и более быстрому восстановлению неврологического статуса. Продемонстрировано накопление ИПСК-НПК в мозге после их внутриартериальной инфузии. Часть клеток взаимодействовала с эндотелием капилляров и, вероятно, способна проникать через ГЭБ.Заключение. Получено экспериментальное подтверждение терапевтической эффективности НПК при ишемическом инсульте при системной, внутриартериальной трансплантации. Отработан и протестирован метод безопасной внутриартериальной инфузии клеточного материала в бассейн внутренней сонной артерии у крыс