Cell and Organ Transplantology

In neurodegenerative processes of the brain, the hippocampus is primarily damaged with subsequent cognitive impairments as a result of increased generation of reactive oxygen species and reactive nitrogen species, which lead to apoptosis and necrosis of neurons. Cell therapy with the use of mesenchymal stromal cells (MSCs) has shown encouraging results regarding endogenous mechanisms of neuroregeneration in response to ischemic injury of brain structures. The work aimed to study the therapeutic potential of MSCs of various origins and sources, MSCs lysate and reference drug citicoline on the energy component of neuronal metabolism, oxidative and nitrosative stress in the rat hippocampus under conditions of cerebral ischemia-reperfusion (IR). Material and methods. The experiment was carried out on 126 Wistar rats with modeled pathology (20-minute IR of the internal carotid arteries), which were injected with MSCs derived from Wharton’s jelly of the human umbilical cord, MSCs derived from human and rat adipose tissues, rat embryonic fibroblasts, MSCs lysate and citicoline immediately after removal of the ligatures. Biochemical parameters of carbohydrate metabolism (glucose, lactate), oxidative (NADPH oxidase activity) and nitrosative stress (NO synthase activity) in the rat hippocampus were determined on days 7 and 14 after IR under the conditions of cerebral IR and on the background of its correction. Results. It was established that during IR in the rat hippocampus of the brain, the content of glucose and lactate increases, the process of aerobic oxidation of glucose is inhibited, anaerobic glycolysis increases, lactic acidosis develops in hippocampal cells, the level of NADPH oxidase activity decreases, and an imbalance occurs in the functioning of the nitrogen monoxide system. A positive effect of human umbilical cord Wharton’s jelly-derived MSC and rat embryonic fibroblasts transplantation, and the use of citicoline on the stabilization of glucose, lactate, NADPH-oxidase and nitric oxide levels was found. Transplantation of human and rat adipose-derived MSCs was significantly less effective than citicoline and demonstrated no statistically significant modulatory effect on biochemical parameters in the hippocampus of experimental animals with IR. Conclusions. Transplantation of the human umbilical cord Wharton’s jelly-derived MSCs was not inferior to the citicoline and, better than other tested MSCs and their lysate, contributed to the recovery of disturbed energy processes (glucose level) and eliminated metabolic acidosis (lactate level) in the hippocampus of rats, i.e. had a positive modulating effect on the oxidant-antioxidant balance (NADPH oxidase activity level).

Serhii Konovalov

Vasyl Moroz

Mykhaylo Yoltukhivskyi

Nataliia Gadzhula

Olena Deryabina

Vitaliy Kordium

Comparative effects of mesenchymal stromal cells of various origins and sources on biochemical parameters in the hippocampus of rats during cerebral ischemia-reperfusion

不同来源和种类的间充质基质细胞对大鼠脑缺血-再灌注期间海马生化参数的比较效应

Antiphospholipid syndrome is one of the most common causes of hypercoagulability. Antiphospholipid syndrome is characterized by thrombotic and obstetric complications, the formation of antiphospholipid antibodies. Molecular phospholipid-protein complexes formed during apoptosis are the target of antiphospholipid antibodies. Considering that endothelial dysfunction plays an important role in the pathogenesis of antiphospholipid syndrome, it is relevant to study the effect of NO synthesis modulators, as well as human mesenchymal stem cells, which have regenerative, anti-inflammatory and immunomodulatory effects on the mechanisms of lung damage in this pathology. Purpose – to investigate the effect of human umbilical cord–derived mesenchymal stem cells and nitric oxide synthase modulators (L-arginine, aminoguanidine) on the level of antiapoptotic markers Bcl-xL and Bcl-xL-BAX and autophagy marker BECN1 in the lungs of mice with experimental antiphospholipid syndrome. Material and methods. Antiphospholipid syndrome was modeled in female BALB/c mice by administering cardiolipin 1.2 mg/kg 4 times with an interval of 14 days. For correction, human umbilical cord-derived mesenchymal stem cells (5×106 cells/kg), L-arginine (25 mg/kg) and aminoguanidine (10 mg/kg) were used, which were administered intraperitoneally once a day for 10 days after the development of APS. To separate proteins from lung tissue, electrophoresis was performed in a polyacrylamide gel in the presence of sodium dodecyl sulfate. For the purpose of immunochemical detection of Bcl-xL, Bcl-xL-BAX, BECN1, proteins were transferred from the gel to a nitrocellulose membrane by electroblotting. Densitometric analysis of immunoreactive zones was performed using the Total Lab TL120 software. Results. In the group of animals with APS, the level of Bcl-xL was lower by 29 %, and Bcl-xL-BAX by 30 %, BECN1 was lower by 42 % compared to the indicators in the animals of the control group. In the group of animals where L-arginine and aminoguanidine were used, an increased level of Bcl-xL protein and Bcl-xL-BAX complex by 36 % and 90 %, respectively, was found, the level of BECN1 was 3 times higher compared to the group of animals with APS. In the group of animals with APS, which were corrected with mesenchymal stem cells, the level of Bcl-xL was 149 % higher, the level of BECN1 increased by 133 % compared to animals with pathology. No significant differences were found in the level of Bcl-xL-BAX. In the group of animals with combined administration of corrective substances – nitric oxide synthase modulators (L-arginine, aminoguanidine) and mesenchymal stem cells – the level of Bcl-xL was 112% higher, and the level of BECN1 was 143% higher compared to animals with APS, while the Bcl-xL-BAX did not differ significantly. Conclusion. In the lungs of mice with antiphospholipid syndrome, inhibition of autophagy and reduced levels of antiapoptotic protein markers were found. With the separate and combined use of human umbilical cord-derived mesenchymal stem cells and nitric oxide synthase modulators (L-arginine, aminoguanidine) for the correction of APS, higher values of antiapoptotic markers Bcl-xL and autophagy protein BECN1 were determined.

N. Mekhno

A. Dovgalyuk

M. Kulitska

O. Dutchak

S. Kornaga

M. Korda

O. Yaremchuk

Human umbilical cord-derived mesenchymal stem cells and nitric oxide synthase modulators inhibit apoptosis and activate autophagy in the lungs of mice with an antiphospholipid syndrome model

人脐带间充质干细胞和一氧化氮合酶调节剂抑制抗磷脂综合征小鼠肺部凋亡并激活自噬

Acute respiratory distress syndrome (ARDS) is a critical state of the body characterized by severe hypoxemia and multiple organ failure. One of the organs that is most often additionally affected due to the systemic inflammatory reaction that occurs in the lungs during ARDS is the kidney. It is known that mesenchymal stem cells (MSCs) can exhibit nephroprotective effects due to their anti-inflammatory and immunomodulatory abilities, but the mechanisms of such therapeutic effects require further elucidation. The purpose is to analyze macrophage polarization in the damaged kidneys of rats with modeled ARDS following the transplantation of human umbilical cord-derived MSCs. Materials and methods. Seventy-two sexually mature male Wistar rats were randomly divided into nine groups: intact animals, 3 days, 7 days and 28 days after ARDS modeling, control-MSC and four correction groups: 24 h ARDS + 2 days MSCs, 4 days of ARDS + 3 days of MSCs, 14 days of ARDS + 14 days of MSCs, 21 days of ARDS + 7 days of MSCs. ARDS was modeled by intranasal administration of lipopolysaccharide (LPS) at a dose of 5 mg/kg. A suspension of MSCs was obtained from the umbilical cord of a healthy donor after a normal delivery by an enzymatic method and administered intraperitoneally at a dose of 1 million cells/kg of body weight. For immunohistochemical determination of the total number of macrophages, pro-inflammatory M1 and anti-inflammatory M2 cells, monoclonal antibodies to CD68, CD86 and CD163 were used, respectively, and the percentage of visual fields occupied by the immunoprecipitate was calculated. Results. Comparative analysis of the percentage of areas occupied by the immunoprecipitate with the corresponding antibodies showed a statistically significant increase in the total number of macrophages (3.8-fold on day 3 of ARDS, 2.8-fold on day 7 of ARDS and 2.4-fold on day 28 of ARDS, respectively), as well as a sharp increase in pro-inflammatory M1 (8.8-fold on day 3 of ARDS, 4.9-fold on day 7 of ARDS, and 4.8-fold on day 28 of ARDS, respectively) and a moderate increase in the percentage of anti-inflammatory M2 cells (1.9-fold on day 3 of ARDS, 2-fold on day 7 of ARDS, and 1.6-fold on day 28 of ARDS, respectively) in modeled ARDS compared to intact animals. This indicates the activation of the inflammatory cascade in the kidneys caused by the development of ARDS. On the other hand, in groups of animals that received MSC correction, a significant decrease, compared to untreated animals, in the total number of macrophages was detected (at 24 h of ARDS + 2 days of MSCs, it was 3.2 times lower than on day 3 of ARDS and ≥ 2 times at later times of the experiment), among which anti-inflammatory cells of the M2 phenotype predominated. Conclusion. Transplanted human umbilical cord-derived MSCs have a pronounced immunomodulatory effect in the affected kidneys of rats with acute respiratory distress syndrome, which is manifested in their ability to change the polarization of macrophages in the anti-inflammatory direction.

I. Palii

S. Kramar

Changes in the macrophage polarization in the kidneys of rats with acute respiratory distress syndrome after transplantation of human umbilical cord-derived mesenchymal stem cell

急性呼吸窘迫综合征大鼠肾脏巨噬细胞极化变化及人脐带间充质干细胞移植的影响

Regenerative injection therapy (synonyms – orthobiology, prolotherapy) is considered the newest direction of orthopedics, which studies the use of cell technologies and new materials to ensure reparative or physiological regeneration in various diseases and injuries of the musculoskeletal system. The substantiation of the therapeutic effectiveness of autologous platelet concentrates, depending on the manufacturing features and characteristics of these biotechnological products, remains an urgent problem. The purpose of the study was to develop the classification and quality and safety criteria of autologous platelet concentrates for regenerative injection therapy in traumatology and orthopedics. Material and methods. A comparative study of 778 autologous platelet concentrates of various types, made from the blood of patients with osteoarthritis and aseptic necrosis of the hip and knee joints due to damage to ligaments and tendons, osteochondrosis of the spine, was conducted. In biotechnological products, the content of platelets and leukocytes was determined, the ratio of platelets and leukocytes among themselves and relative to their content in peripheral blood was calculated, respectively. During the production of autologous platelet concentrates, the visual characteristics of cell sediment and plasma were evaluated. Products of platelet cryolysates were subject to microbiological testing. Results. The classification of autologous platelet concentrates according to the concentration of platelets and leukocytes was developed, as well as the quality and comprehensive safety criteria of cellular forms of autologous platelet concentrates were determined: platelet index of autologous platelet concentrate, leukocyte index of autologous platelet concentrate, leukocyte-platelet index of autologous platelet concentrate. Visual characteristics of platelet concentrates were established: “ideal”, “classic”, “erythrocyte”, “low cell” and “alimentary” phenotype. Based on the results of a microbiological study, the safety of platelet concentrates for intra-articular administration to orthopedic and trauma patients was established. Conclusions. The developed classification of biotechnological products from human peripheral blood, as well as their quantitative and qualitative criteria, is the basis for the development of differentiated and personalized approaches to their use in diseases and injuries of the musculoskeletal system.

Ye. Holiuk

S. Strafun

O. Lushchii

T. Ostapenko

V. Smorzhevskyi

Development of classification and criteria of quality and safety of autologous platelet concentrates for regenerative injection therapy in traumatology and orthopedics

创伤骨科再生注射治疗自体血小板浓缩物质量与安全分类标准的制定

Publication Information	Publisher: Institute of Cell Therapy，Publishing cycle: ，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 2019，Proportion of original research papers: 0.00%，Self Citation Rate:N.A.， Gold OA Rate: 0.00%

Cell and Organ Transplantology

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Comparative effects of mesenchymal stromal cells of various origins and sources on biochemical parameters in the hippocampus of rats during cerebral ischemia-reperfusion

Comparative effects of mesenchymal stromal cells of various origins and sources on biochemical parameters in the hippocampus of rats during cerebral ischemia-reperfusion

Human umbilical cord-derived mesenchymal stem cells and nitric oxide synthase modulators inhibit apoptosis and activate autophagy in the lungs of mice with an antiphospholipid syndrome model

Changes in the macrophage polarization in the kidneys of rats with acute respiratory distress syndrome after transplantation of human umbilical cord-derived mesenchymal stem cell

Development of classification and criteria of quality and safety of autologous platelet concentrates for regenerative injection therapy in traumatology and orthopedics

Comparative effects of mesenchymal stromal cells of various origins and sources on biochemical parameters in the hippocampus of rats during cerebral ischemia-reperfusion

Comparative effects of mesenchymal stromal cells of various origins and sources on biochemical parameters in the hippocampus of rats during cerebral ischemia-reperfusion

Human umbilical cord-derived mesenchymal stem cells and nitric oxide synthase modulators inhibit apoptosis and activate autophagy in the lungs of mice with an antiphospholipid syndrome model

Changes in the macrophage polarization in the kidneys of rats with acute respiratory distress syndrome after transplantation of human umbilical cord-derived mesenchymal stem cell

Development of classification and criteria of quality and safety of autologous platelet concentrates for regenerative injection therapy in traumatology and orthopedics

ISSN	2308-3794, 2311-021X
h-index	2