scholarly journals PARKINSONISM SYNDROME FORMATION IN EXPERIMENTAL ANIMALS. NEUROINFLAMMATORY PENUMBRA

2021 ◽  
Vol 20 (4) ◽  
pp. 53-60
Author(s):  
A.V. Boika ◽  
◽  
N. Y. Aleinikava ◽  
V.V. Ponomarev ◽  
A.M. Ustsiamchuk ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Homovanillic Acid ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Dopamine Metabolism ◽  
Laboratory Animals ◽  
Control Group ◽  
Motor Disorders ◽  
Post Transplantation ◽  
Potential Therapeutic Target ◽  
Parallel Increase

Much valuable information about the development of Parkinson’s disease (PD) has been obtained from studies on the laboratory animals. Objectives. To compare the development of neurotoxic and neuroinflammatory parkinsonism syndrome in laboratory animals. Material and methods. The number of rats in the group of neuroinflammatory model of parkinsonism syndrome (lipopolysaccharide) was 6, and in the group of neurotoxic model (rotenone) - 20. The control group consisted of 5 animals. The study was approved by the independent Ethics Committee. The development dynamics of parkinsonism syndrome of neurotoxic and neuroinflammatory genesis was assessed in the study of the motor activity of animals, as well as in the laboratory study of biomarkers of dopamine metabolism (dopamine and homovanillic acid) in blood serum and cerebrospinal fluid obtained in 7 and 21 days after the first administration of rotenone or lipopolysaccharide, and also after a single intravenous injection of allogeneic (rat) multipotent mesenchymal stromal cells (MMSC) carried out after 9 injections of rotenone. Results. A decrease in the levels of dopamine and homovanillic acid has been shown in laboratory animals on the development of Parkinson’s syndrome. In rats with a neuroinflammatory model of parkinsonism syndrome, a pre-motor stage of motor disorders development has been laboratorially confirmed. During the first weeks after the introduction of MMSC, regression of the motor symptoms of neurotoxic parkinsonism syndrome and a parallel increase in dopamine and homovanillic acid are determined. Conclusions. The effectiveness of MMSC in the early post-transplantation period is associated with the paracrine effect. It is proposed to call activated microglia, a potential therapeutic target in PD, neuroinflammatory penumbra.

scholarly journals Homing and Engraftment of Intravenously Administered Equine Cord Blood-Derived Multipotent Mesenchymal Stromal Cells to Surgically Created Cutaneous Wound in Horses: A Pilot Project

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1162
Author(s):  
Suzanne J. K. Mund ◽  
Eiko Kawamura ◽  
Awang Hazmi Awang-Junaidi ◽  
John Campbell ◽  
Bruce Wobeser ◽  
...  
Keyword(s):  
Cord Blood ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Adverse Reactions ◽  
Pilot Project ◽  
Multipotent Mesenchymal Stromal Cells ◽  
The Body ◽  
Laboratory Animals ◽  
Clinical Safety ◽  
Allogeneic Mscs

Limb wounds on horses are often slow to heal and are prone to developing exuberant granulation tissue (EGT) and close primarily through epithelialization, which results in a cosmetically inferior and non-durable repair. In contrast, wounds on the body heal rapidly and primarily through contraction and rarely develop EGT. Intravenous (IV) multipotent mesenchymal stromal cells (MSCs) are promising. They home and engraft to cutaneous wounds and promote healing in laboratory animals, but this has not been demonstrated in horses. Furthermore, the clinical safety of administering >1.00 × 108 allogeneic MSCs IV to a horse has not been determined. A proof-of-principle pilot project was performed with two horses that were administered 1.02 × 108 fluorescently labeled allogeneic cord blood-derived MSCs (CB-MSCs) following wound creation on the forelimb and thorax. Wounds and contralateral non-wounded skin were sequentially biopsied on days 0, 1, 2, 7, 14, and 33 and evaluated with confocal microscopy to determine presence of homing and engraftment. Results confirmed preferential homing and engraftment to wounds with persistence of CB-MSCs at 33 days following wound creation, without clinically adverse reactions to the infusion. The absence of overt adverse reactions allows further studies to determine effects of IV CB-MSCs on equine wound healing.

scholarly journals Possibility of using combined transplantation of multipotent mesenchymal stromal cells and hepatic stellate cells to activate reparative liver regeneration in mature and old organism

2020 ◽  
Vol 22 ◽  
pp. 01004
Author(s):  
Irina Maklakova ◽  
Dmitry Grebnev ◽  
Victoria Vakhrusheva ◽  
Ekaterina Petrunina
Keyword(s):  
Body Weight ◽  
Liver Regeneration ◽  
Cell Transplantation ◽  
Stromal Cells ◽  
Age Groups ◽  
Stellate Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Laboratory Animals ◽  
Subtotal Resection ◽  
Intracellular Regeneration

The aim of the study was to examine the effect of combined transplantation of multipotent mesenchymal stromal (MMSC) and hepatic stellate (HSC) cells on liver regeneration after resection. Research has been carried out on laboratory animals of mature and old age. After the subtotal resection of the liver, MMSC and HSC were introduced in the tail vein in the amount of 4 million cl/kg of body weight and 9 million cl/kg of body weight respectively. Evaluation of reparative liver regeneration was performed on the 1st, 3rd, 7th days after subtotal liver resection. Features of reparative liver regeneration in mature and old organism were revealed. In mature organism against the background of combined cell transplantation, regeneration activation is achieved by increasing cellular and intracellular regeneration mechanisms. In this case, the old organism responds to cell transplantation by activating only intracellular mechanisms. In both age groups, decreased mutagenesis and inhibition of programmed cell death against the background of MMSC cotransplantation and HSC were observed.

scholarly journals Activation of reparative liver regeneration following the combined transplantation of multipotent mesenchymal stromal cells and hepatic stellate cells

2021 ◽  
Vol 102 (5) ◽  
pp. 669-677
Author(s):  
I Yu Maklakova ◽  
D Yu Grebnev ◽  
A V Osipenko
Keyword(s):  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Hepatic Stellate Cells ◽  
Comparison Group ◽  
Stellate Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Control Group ◽  
Nacl Solution

Aim. To study the effect of combined transplantation of multipotent mesenchymal stromal and hepatic stellate cells on the reparative liver regeneration. Methods. Laboratory mice were given intravenous administration of multipotent mesenchymal stromal and hepatic stellate cells after partial hepatectomy. The mice were divided into four groups: control, experimental 1 (injection of multipotent mesenchymal stromal cells), experimental 2 (co-transplantation of multipotent mesenchymal stromal cells and hepatic stellate cells), the comparison group. Comparison of the experimental groups with the control group and the comparison group was carried out. Each group consisted of 14 animals. The control and experimental groups underwent partial hepatectomy. The experimental mice were injected with the cells into the lateral tail vein 1 hour after the operation. Multipotent mesenchymal stromal cells were administered at a dose of 4 million cells/kg (120 thousand cells/mouse), hepatic stellate cells in the amount of 9 million cells/kg (270 thousand cells/mouse), suspended in 0.2 ml 0.9% NaCl solution. The control group animals were injected with 0.2 ml 0.9% NaCl solution into the lateral tail vein. The comparison group consisted of mice without partial hepatectomy, injected with 0.2 ml 0.9% NaCl solution. To assess reparative regeneration of the liver, morphometric parameters of the liver, blood biochemical parameters on the 3rd and 7th days after partial hepatectomy were studied. The severity of apoptosis was assessed by the immunohistochemical method, the activity of deoxyribonucleic acid (DNA) repair enzymes of the poly (ADP-ribose) polymerases was determined by flow cytometry. The number of micronucleated hepatocytes was also determined. The hepatocyte growth factor (HGF) content was measured by using an enzyme-linked immunosorbent assay in serum. The significance of differences in the compared samples was determined by using the Student's t-test. Statistical data processing was performed by using the SPSS Statistics software version 17.0. Results. It was found that the combined transplantation of multipotent mesenchymal stromal and stellate liver cells causes restoration of the activity of alanine aminotransferase (a decrease of 30.3%, p=0.016), aspartate aminotransferase (a decrease of 27.7%, p=0.021), alkaline phosphatase (a decrease of 21.1%, p=0.036), an increase in the protein synthetic function of the liver (increase in albumin level by 36.6%, p=0.009), an increase in hepatocyte growth factor level by 74.3%. These changes were accompanied by the restoration of liver morphometric parameters: there was an increase in the mitotic activity of hepatocytes by 28.7% (p=0.008), the nuclear area of hepatocytes by 26.7% (p=0.006), the number of binucleated hepatocytes by 26.1% (p=0.004), which led to the restoration of liver mass. There was a decrease in the level of apoptosis by 28.8% (p=0.006) and a decrease in the number of micronucleated hepatocytes by 22.7% (p=0.001) compared with the control group, which may be related to an increase in the activity of Poly (ADP-ribose) polymerase repair enzymes detected in the study. The deviations were presented as a difference relative to the indicators of the control group (operated animals that were injected with 0.9% NaCl solution). Conclusion. Combined transplantation of multipotent mesenchymal stromal and hepatic stellate cells activates reparative liver regeneration after partial hepatectomy.Keywords: multipotent mesenchymal stromal cells, MSC, hepatic stellate cells, HSC, liver regeneration, partial hepatectomy.

THE STUDY OF MMSC HOMING AFTER LIVER RESECTION

2019 ◽  
pp. 40-45
Author(s):  
И.Ю. Маклакова ◽  
Д.Ю. Гребнев ◽  
В.Ч. Юсупова ◽  
Е.А. Примакова
Keyword(s):  
Liver Resection ◽  
Portal Vein ◽  
Hepatic Artery ◽  
Stromal Cells ◽  
Peripheral Blood ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Cell Number ◽  
Laboratory Animals ◽  
Cell Injection ◽  
Physiological Conditions

Цель работы - изучение направленного движения мультипотентных мезенхимальных стромальных клеток (ММСК), выделенных из плаценты, в различные органы и ткани лабораторных животных в физиологических условиях и после субтотальной резекции печени. Методика. Клеточную культуру ММСК получали из хориона плаценты лабораторных крыс. Культивирование ММСК проводилось в условиях СО2- инкубатора при температуре 37 ºC с содержанием углекислого газа 5% и влажностью 90%. Замену среды проводили каждые 3-4 сут до достижения клетками 70-80 % конфлюэнтности. При формировании соответствующего монослоя осуществлялся пересев клеток. При трансплантации лабораторным животным была использована культура ММСК 3-го пассажа. Введение клеток производили сразу после выполнения субтотальной резекции печени. Резекция 70% печени у крыс выполнена по методике G.M. Higgins, R.M. Anderson. Введение ММСК, меченых акридиновым оранжевым, осуществляли внутривенно, интраперитонеально, в печеночную артерию, в портальную вену в дозе 4 млн кл/кг. массы тела. Анализ распределения ММСК проводили через 3 и 24 ч. Результаты. Показано, что через 1 сут после введения клеток ложно-оперированным животным не отмечено существенных изменений распределения ММСК по сравнению с их распределением через 3 ч. Однако если введение клеток сопряжено с оперативным вмешательством (лапаротомия для обеспечения введения клеток в v. portae и a. hepatica) происходит снижение их количества в периферической крови. Через 1 сут после резекции печени в изучаемых органах и тканях (периферическая кровь, легкое, селезенка, костный мозг, тонкий кишечник, почка) содержание трансплантированных ММСК ниже по сравнению с их количеством в тот же период времени в данных органах и тканях без резекции печени. Обращает внимание значительное увеличение количества введенных клеток в печени после ее резекции как через 3 ч, так и через 24 ч по сравнению с физиологическими условиями. Заключение. Отмечено значительное увеличение количества клеток в печени после ее резекции вне зависимости от способа введения. Внутрибрюшинный способ введения клеток показал низкую эффективность доставки клеток в органы и ткани организма. The aim was to study migration of multipotent mesenchymal stromal cells (MSCS) isolated from the placenta to various organs and tissues of laboratory animals under the physiological conditions and after subtotal liver resection. Method. The MMSC cells for culturing were obtained from the rat placental chorion. MMSCs were cultured in a CO2 incubator at 37 oC, 5% CO2, and 90% humidity. The medium was replaced every 3-4 days until the cells reached 70-80 % confluence. Upon formation of an appropriate monolayer the cells were passed. The third passage culture of MMSC was used for transplantation to laboratory animals. Cells were injected immediately after subtotal liver resection. The 70% rat liver resection was performed according to the method of G.M. Higgins and R.M. Anderson. The acridine orange labeled MMSC were injected intravenously, intraperitoneally, into the hepatic artery, and into the portal vein at a dose of 4x106 cells/kg body weight. The MMSC distribution was analyzed at 3 and 24 hours. Results. In 24 h after the cell injection in the absence of liver resection, no significant changes were observed in the MMSCs distribution compared to their distribution in 3 hours. However, when the cell injection was associated with a surgery (laparotomy to ensure the cell injection into the portal vein and hepatic artery) the cell number was decreased in the peripheral blood. At one day after liver resection, the content of transplanted MMSCs was lower in the studied organs and tissues (peripheral blood, lung, spleen, bone marrow, small intestine, and kidney) compared to the respective values without liver resection in the same period. Noticeably, the number of injected cells was significantly increased in the liver at both 3 and 24 hours after resection compared to the physiological conditions. Conclusion. The number of cells was significantly increased in the liver after resection regardless of the cell administration route. Intraperitoneal cell injection showed a low effectiveness of cell delivery to organs and tissues.

THE EFFECT OF MULTIPOTENT MESENCHYMAL STROMAL CELLS TRANSPLANTATION ON LIVER MORPHOMETRIC PARAMETERS OF MATURE AND OLD LABORATORY ANIMALS WITH TOXIC HEPATITIS

2020 ◽  
pp. 55-60
Author(s):  
И. Ю. Маклакова ◽  
Д. Ю. Гребнев ◽  
В. Ч. Юсупова ◽  
Е. М. Петрунина
Keyword(s):  
Mitotic Activity ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Toxic Hepatitis ◽  
Age Groups ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Morphometric Parameters ◽  
Laboratory Animals ◽  
Intracellular Regeneration ◽  
Hepatocyte Nucleus

Цель - изучение влияния трансплантации мультипотентных мезенхимальных стромальных клеток (ММСК) на морфометрические показатели печени зрелых и старых лабораторных животных в условиях токсического гепатита. Материал и методы. Эксперименты выполнены на зрелых и старых мышах-самцах. Токсический гепатит вызывали путем внутрибрюшинного введения CClв дозе 50 мкг/кг. Трансплантация клеток осуществлялась в хвостовую вену через 1 ч после введения четыреххлористого углерода однократно. Исследовалось влияние ММСК на морфометрические показатели печени в физиологических условиях и условиях токсического гепатита на 1-, 3-, 7-е сутки после трансплантации клеток. Результаты. У зрелых лабораторных животных на 3-и сутки после введения ММСК на фоне токсического гепатита обнаружено увеличение митотической активности, повышение количества гепатоцитов, площади ядра гепатоцитов и ядерноцитоплазматического индекса. В то же время, у старых лабораторных животных выявлено лишь увеличение площади ядра гепатоцитов и ядерно-цитоплазматического индекса. На 7-е сутки после введения ММСК на фоне токсического гепатита в обеих возрастных группах выявлены активация митотической активности, повышение количества гепатоцитов, увеличение площади ядра гепатоцитов и ядерно-цитоплазматического индекса. Выводы. Изменение морфометрических показателей печени у зрелых и старых лабораторных животных реализуется через механизмы как клеточной, так и внутриклеточной регенерации. При этом у старых лабораторных животных на 3-и сутки после введения ММСК выявлена активация лишь внутриклеточной регенерации, в то время как у зрелых лабораторных животных имеет место повышение клеточной и внутриклеточной регенерации гепатоцитов. В более поздние сроки в обеих изучаемых возрастных группах изменение основных морфометрических показателей печени реализуется через активацию как клеточной, так и внутриклеточной регенерации. Objective - to study the influence of multipotent mesenchymal stromal cells (MMSC) transplantation on morphometric parameters of the liver of mature and old laboratory animals with toxic hepatitis. Material and methods. The experiments were performed on mature and old male mice. Toxic hepatitis was caused by intraperitoneal administration of CCl4 at a dose of 50 μg/kg. The cells were transplanted via the tail vein 1 hour after administration of a single dose of carbon tetrachloride. The effect of MMSC on liver morphometric parameters in physiological conditions and after toxic hepatitis development was studied on days 1, 3, 7 after cell transplantation. Results. An increase in mitotic activity, an increase in the number of hepatocytes, hepatocyte nucleus area, and nuclear cytoplasmic index were found in mature laboratory animals with toxic hepatitis on the 3 day after the introduction of MMSC. At the same time, only an increase in the area of hepatocyte nucleus and nuclear cytoplasmic index was revealed in old laboratory animals. On the 7 day after the introduction of MMSC to the animals with toxic hepatitis, both age groups demonstrated activation of mitotic activity, an increase in the number of hepatocytes, an increase in the area of hepatocyte nucleus and nuclear cytoplasmic index. Conclusions. Changes in liver morphometric parameters in mature and old laboratory animals are realized through mechanisms of both cellular and intracellular regeneration. In addition, the activation of only intracellular regeneration was found in old laboratory animals on the 3rd day after the introduction of MMSC, while in mature laboratory animals there was an increase in cellular and intracellular regeneration of hepatocytes. In later periods in both studied age groups, the change in the main liver morphometric parameters is realized through the activation of both cellular and intracellular regeneration.

scholarly journals Treatment of cranial cruciate ligament injuries in dogs using a combination of tibial tuberosity advancement procedure and autologous mesenchymal stem cells/multipotent mesenchymal stromal cells – A pilot study

2021 ◽  
Author(s):  
Saša Koprivec ◽  
Marko Novak ◽  
Stanislav Bernik ◽  
Metka Voga ◽  
Luka Mohorič ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pilot Study ◽  
Bone Tissue ◽  
Silk Fibroin ◽  
Stromal Cells ◽  
Cruciate Ligament ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Control Group ◽  
Cranial Cruciate Ligament ◽  
Silk Fibroin Scaffold

AbstractIn the present pilot study, we evaluated different supplemental therapies using autologous multipotent mesenchymal stromal cells (MMSCs) for the treatment of cranial cruciate ligament defects in dogs. We used tibial tuberosity advancement (TTA) and augmented it by supportive therapy with MMSCs in three patient groups. In the first patient group, the dogs were injected with MMSCs directly into the treated stifle one month after surgery. In the second group, MMSCs were delivered in a silk fibroin scaffold which was placed in the osteotomy gap during surgery. In the third group, MMSCs were first mixed with bone tissue and blood from the patient and delivered into the osteotomy gap during surgery. In the control group, patients underwent the TTA procedure but did not receive MMSC treatment. In the group of patients who received cells in the silk fibroin scaffold during surgery, the osteotomy gap did not heal, presumably due to the low absorption of silk fibroin. Patients who received MMSCs mixed with bone tissue and blood during surgery into the osteotomy gap recovered clinically faster and had better healing of the osteotomy gap than dogs from the other two treated groups and from the control group, as assessed by clinical examination and quantification of radiographs. In conclusion, dogs that received stem cells directly into the osteotomy gap (Group 3) recovered faster compared to dogs from Groups 1 (MMSCs injected into the joint one month after surgery), 2 (cells implanted into the osteotomy gap in a silk fibroin scaffold), and the control group that did not receive additional MMSCs treatment.

scholarly journals Dynamics of Cytokines Concentration in the Blood Plasma of Patients after Multipotent Mesenchymal Stromal Cells Administration for Graft Versus Host Disease Prevention

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1101-1101
Author(s):  
Nataliya A. Petinati ◽  
Julia O Davydova ◽  
Kseniya A. Nikiforova ◽  
Alexey Bigildeev ◽  
Georgiy Arapidi ◽  
...  
Keyword(s):  
T Cells ◽  
Mesenchymal Stromal Cells ◽  
Graft Versus Host Disease ◽  
Stromal Cells ◽  
Peripheral Blood ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Control Group ◽  
Allogeneic Bone ◽  
Host Disease ◽  
Graft Versus Host

Abstract Introduction Despite the large number of clinical studies on the use of multipotent mesenchymal stromal cells (MSCs) for the treatment and prevention of graft-versus-host disease (GVHD), the mechanism of their action in the organism is not well understood. The known data refer either to clinical effects or obtained in vitro. Due to the immunomodulatory effect of MSCs in the body, subpopulations of T cells and the concentration of cytokines involved in the immune response can change. The role of T cells and certain cytokines (TNF alpha, IL6, IL8, etc.) in the pathophysiology of GVHD is described. The aim of this investigation was to study the composition of T cells subpopulations and the concentration of cytokines in the peripheral blood of patients who received MSCs for GVHD prophylaxis. Methods The study included 21 patients who received hematopoietic stem cells donor's derived MSCs for the prevention of GVHD as part of the ClinicalTrials.gov Identifier NCT01941394 trial. The control group included 16 patients who did not receive MSCs. After signing informed consent, blood samples were taken from all patients during routine examinations on the day of restoration of the number of leukocytes to 1000 in μl (day 0), after 3 and after 30 days. MSCs were injected on day 0. None of the patients developed GVHD during this time. To analyze plasma cytokines and chemokines, the Bio-Plex Pro Human Cytokine Panel kit, 27-Plex (BioRad) was used, to determine the concentrations of IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL- 6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, bFGF, Eotaxin, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1 (MCAF), MIP-1α, MIP-1β, PDGF-bb, RANTES, TNF-α, VEGF according to manufacturer's recommendations. Forward and side scattering parameters determined the peripheral blood lymphocytes population and then CD4+ or CD8+ lymphocytes were gated. For each of this population the composition of memory cells subset were determined by flow cytometry. Results Significant differences were found between the 2 groups only on day 30 in the concentration of IL8 (17.0±3.2 pg/ml in the control group versus 32.8±4.1 pg/ml in the MSC group, p<0.0001). It has been shown that 30 days after MSCs, the number of CD4+ T cells in the peripheral blood of patients significantly increases compared to the group without MSCs (CD4 CM 38.9±9.0 vs 22.4±7.8, CD4 TM 97.0±32.5 vs 91.0±43.2, CD4 TE 5.0±1.9 vs 1.4±1.0, CD4 EM 34.6±20.1 vs 19.9±7.9, CD4CD25+ 27.6±6.6 vs 12.9±5.0). These cells produce IL8, which play an important role in immune cell homeostasis by activating antimicrobial neutrophils. Without the introduction of MSCs, the concentration of this protective against GVHD cytokine practically did not change within a month, whereas after the introduction of MSCs, it gradually increased almost 2 times. However, the dynamics of changes in the levels of the studied cytokines differed greatly between the 2 groups (Table). The concentration of IP10, which is involved in the development of GVHD, increased significantly faster and stronger in the group without MSCs. An increase in the concentration of other investigated cytokines associated with the activation of macrophages (MCP-1, MIP-1a, MIP-1b) did not depend on the MSCs administration. At the same time, in the MSC group, the concentration of the growth factor PDGF-bb necessary for the HSC proliferation increased significantly more actively. The IL9 concentration on day 0 was comparable to the level in healthy donors, and then gradually increased in both groups and after 30 days it was significantly higher than on day 0 in the MSC administration group. The concentration of G-CSF changed in a similar way. Conclusion Changes in the dynamics of T cells subpopulations and the concentration of cytokines in the blood after MSCs administration contribute to a faster recovery of patients after allogeneic bone marrow transplantation. The work were supported by the Russian Foundation for Basic Research, Project No. 19-29-04023. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Course correction of adjuvant arthritis with cryopreserved multipotent mesenchymal stromal cells

2021 ◽  
Vol 12 (3) ◽  
pp. 545-553
Author(s):  
D. B. Vvedenskyi ◽  
N. O. Volkova ◽  
M. S. Yukhta ◽  
N. O. Ashukina ◽  
A. M. Goltsev
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Adjuvant Arthritis ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Cyclooxygenase 2 ◽  
Biologically Active ◽  
Cartilage Tissue ◽  
Control Group ◽  
Regenerative Processes ◽  
And Cartilage

Rheumatoid arthritis is an inflammatory autoimmune disease that occurs as a result of impaired immune tolerance, leading to an aberrant immune response to autologous antigens. Multipotent mesenchymal stromal cells (MMSCs) and the biologically active substances they produce can promote the activation of regenerative processes in the organism not only by direct cell differentiation, but also due to their inherent trophic and immunosuppressive potentials. The aim of the study was to experimentally evaluate changes in the course of the acute phase of adjuvant arthritis upon local and generalized administration of cryopreserved MMSCs from adipose and cartilage tissues. The results of histological, imunohistochemical and biochemical studies showed that the animals of the control group throughout the observation period developed an inflammatory process, which manifested in joint swelling (increased arthritis index), leukocytosis, spread of chondrocyte-free zones, weakening of staining, loss of clarity of cartilage tissue contours, increased content of cyclooxygenase-2, reduced glycosaminoglycan content and total antioxidant defense system activity. At the same time, the local administration of cryopreserved MMSCs from adipose and cartilage tissues contributed to the normalization of the structural and functional organization, content of glycosaminoglycans and cyclooxygenase-2 with complete recovery of blood parameters. Less pronounced regeneration processes in articular cartilage occurred under generalized administration of cryopreserved MMSCs from adipose and cartilage tissues in comparison with the local method. However, the difference between the control and experimental groups indicates the ability of cryopreserved MMSCs to influence the intensity of regenerative processes in damaged cartilage tissue with both methods of administration. Comparative evaluation of the use of cryopreserved MMSCs from adipose and cartilage tissues showed the absence of significant changes in the studied indicators. These data can be used to substantiate and develop methods of arthritis treatment in clinical practice.

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