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.

scholarly journals Three-dimensional cartilage-derived construct derived from multipotent mesenchymal stromal cells

2020 ◽  
Vol 22 ◽  
pp. 02014
Author(s):  
Oleg Makeyev ◽  
Arteom Korotkov ◽  
Svetlana Kostyukova ◽  
Daria Sichkar ◽  
Elizaveta Yakovleva
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Three Dimensional ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Cartilage Tissue ◽  
Cartilage Surface ◽  
Initial Stage ◽  
Conventional Drug ◽  
Surgical Methods ◽  
Further Development

Damage to the cartilage surface of the joints is a common pathology. Conventional drug therapies are effective only at the initial stage of the disease and only slow down the further development of the disease. In subsequent stages, it is necessary to apply surgical methods from replacing a defect to complete prosthetics of a damaged joint. In order to replace defects in cartilage tissue, a three-dimensional bioequivalent was created based on autologous multipotent mesenchymal stromal cells.

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.

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.

Differentiation of multipotent mesenchymal stromal cells of human bone marrow into cells of cartilage tissue by culturing in three-dimensional OPLA scaffolds

2007 ◽  
Vol 1 (2) ◽  
pp. 125-132 ◽  
Author(s):  
A. S. Teplyashin ◽  
S. V. Korjikova ◽  
S. Z. Sharifullina ◽  
M. S. Rostovskaya ◽  
N. I. Chupikova ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Three Dimensional ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Cartilage Tissue

scholarly journals Assessment of effectiveness of cryopreserved multipotent mesenchymal stromal cells from adipose tissue in adjuvant arthritis treatment

2020 ◽  
Vol 30 (3) ◽  
pp. 292-292
Author(s):  
Dmytro Vvedenskyy ◽  
◽  
Nataliia Volkova ◽  
Anatoliy Goltsev ◽  
◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Adjuvant Arthritis ◽  
Multipotent Mesenchymal Stromal Cells

scholarly journals Multipotent mesenchymal stromal cells are sensitive to thermic stress – potential implications for therapeutic hyperthermia

2020 ◽  
Vol 37 (1) ◽  
pp. 430-441
Author(s):  
Alexander Rühle ◽  
Andreas Thomsen ◽  
Rainer Saffrich ◽  
Maren Voglstätter ◽  
Birgit Bieber ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Therapeutic Hyperthermia

scholarly journals The clinical efficacy of arthroscopic therapy with knee infrapatellar fat pad cell concentrates in treating knee cartilage lesion: a prospective, randomized, and controlled study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yiqin Zhou ◽  
Haobo Li ◽  
Dong Xiang ◽  
Jiahua Shao ◽  
Qiwei Fu ◽  
...  
Keyword(s):  
Clinical Efficacy ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Knee Arthroscopy ◽  
Infrapatellar Fat Pad ◽  
Control Group ◽  
Knee Cartilage ◽  
Fat Pad ◽  
Group 12 ◽  
Significant Difference

Abstract Introduction To evaluate the clinical efficacy of arthroscopic therapy with infrapatellar fat pad cell concentrates in treating knee cartilage lesions, we conducted a prospective randomized single-blind clinical study of controlled method. Methods Sixty cases from Shanghai Changzheng Hospital from April 2018 to December 2019 were chosen and randomly divided into 2 groups equally. Patients in the experiment group were treated through knee arthroscopy with knee infrapatellar fat pad cell concentrates containing mesenchymal stromal cells, while patients in the control group were treated through regular knee arthroscopic therapy. VAS and WOMAC scores were assessed at pre-operation, and 6 weeks, 12 weeks, 6 months, and 12 months after intervention. MORCART scores were assessed at pre-operation and 12 months after intervention. Results Twenty-nine cases in the experiment group and 28 cases in the control group were followed up. No significant difference in VAS, WOMAC, and MOCART scores were found between the two groups before surgery (P > 0.05). The WOMAC total and WOMAC function scores of the experiment group were significantly lower than those of the control group 6 months and 12 months after surgery (P < 0.05). The VAS rest and VAS motion scores of the experiment group were found significantly lower than those of the control group 12 months after surgery (P < 0.05). The MOCART scores of the experiment group were found significantly higher compared with the control group 12 months after surgery (P < 0.05). No significant difference in WOMAC stiffness scores were found between the two groups. Conclusions The short-term results of our study are encouraging and demonstrate that knee arthroscopy with infrapatellar fat pad cell concentrates containing mesenchymal stromal cells is safe and provides assistance in reducing pain and improving function in patients with knee cartilage lesions. Trial registration ChiCTR1800015379. Registered on 27 March 2018, http://www.chictr.org.cn/showproj.aspx?proj=25901.

scholarly journals 3D-printed nerve guidance conduits multi-functionalized with canine multipotent mesenchymal stromal cells promote neuroregeneration after sciatic nerve injury in rats

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Diego Noé Rodríguez-Sánchez ◽  
Giovana Boff Araujo Pinto ◽  
Luciana Politti Cartarozzi ◽  
Alexandre Leite Rodrigues de Oliveira ◽  
Ana Livia Carvalho Bovolato ◽  
...  
Keyword(s):  
Growth Factor ◽  
Sciatic Nerve ◽  
Nerve Injury ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Sciatic Nerve Injury ◽  
Motor Deficits ◽  
3D Printed

Abstract Background Nerve injuries are debilitating, leading to long-term motor deficits. Remyelination and axonal growth are supported and enhanced by growth factor and cytokines. Combination of nerve guidance conduits (NGCs) with adipose-tissue-derived multipotent mesenchymal stromal cells (AdMSCs) has been performing promising strategy for nerve regeneration. Methods 3D-printed polycaprolactone (PCL)-NGCs were fabricated. Wistar rats subjected to critical sciatic nerve damage (12-mm gap) were divided into sham, autograft, PCL (empty NGC), and PCL + MSCs (NGC multi-functionalized with 106 canine AdMSCs embedded in heterologous fibrin biopolymer) groups. In vitro, the cells were characterized and directly stimulated with interferon-gamma to evaluate their neuroregeneration potential. In vivo, the sciatic and tibial functional indices were evaluated for 12 weeks. Gait analysis and nerve conduction velocity were analyzed after 8 and 12 weeks. Morphometric analysis was performed after 8 and 12 weeks following lesion development. Real-time PCR was performed to evaluate the neurotrophic factors BDNF, GDNF, and HGF, and the cytokine and IL-10. Immunohistochemical analysis for the p75NTR neurotrophic receptor, S100, and neurofilament was performed with the sciatic nerve. Results The inflammatory environment in vitro have increased the expression of neurotrophins BDNF, GDNF, HGF, and IL-10 in canine AdMSCs. Nerve guidance conduits multi-functionalized with canine AdMSCs embedded in HFB improved functional motor and electrophysiological recovery compared with PCL group after 12 weeks. However, the results were not significantly different than those obtained using autografts. These findings were associated with a shift in the regeneration process towards the formation of myelinated fibers. Increased immunostaining of BDNF, GDNF, and growth factor receptor p75NTR was associated with the upregulation of BDNF, GDNF, and HGF in the spinal cord of the PCL + MSCs group. A trend demonstrating higher reactivity of Schwann cells and axonal branching in the sciatic nerve was observed, and canine AdMSCs were engrafted at 30 days following repair. Conclusions 3D-printed NGCs multi-functionalized with canine AdMSCs embedded in heterologous fibrin biopolymer as cell scaffold exerted neuroregenerative effects. Our multimodal approach supports the trophic microenvironment, resulting in a pro-regenerative state after critical sciatic nerve injury in rats.

Alterations in multipotent mesenchymal stromal cells from the bone marrow of acute myeloid leukemia patients at diagnosis and during treatment

2019 ◽  
Vol 60 (8) ◽  
pp. 2042-2049
Author(s):  
Irina N. Shipounova ◽  
Nataliya A. Petinati ◽  
Alexey E. Bigildeev ◽  
Tamara V. Sorokina ◽  
Larisa A. Kuzmina ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Myeloid Leukemia ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Acute Myeloid
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