scholarly journals Effect of Metformin on Viability, Morphology, and Ultrastructure of Mouse Bone Marrow-Derived Multipotent Mesenchymal Stromal Cells and Balb/3T3 Embryonic Fibroblast Cell Line

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Agnieszka Śmieszek ◽  
Aleksandra Czyrek ◽  
Katarzyna Basinska ◽  
Justyna Trynda ◽  
Aneta Skaradzińska ◽  
...  

Metformin, a popular drug used to treat diabetes, has recently gained attention as a potentially useful therapeutic agent for treating cancer. In our research metformin was added toin vitrocultures of bone marrow-derived multipotent mesenchymal stromal cells (BMSCs) and Balb/3T3 fibroblast at concentration of 1 mM, 5 mM, and 10 mM. Obtained results indicated that metformin negatively affected proliferation activity of investigated cells. The drug triggered the formation of autophagosomes and apoptotic bodies in all tested cultures. Additionally, we focused on determination of expression of genes involved in insulin-like growth factor 2 (IGF2) signaling pathway. The most striking finding was that the mRNA level of IGF2 was constant in both BMSCs and Balb/3T3. Further, the analysis of IGF2 concentration in cell supernatants showed that it decreased in BMSC cultures after 5 and 10 mM metformin treatments. In case of Balb/3T3 the concentration of IGF2 in culture supernatants decreased after 1 and 5 mM and increased after 10 mM of metformin. Our results suggest that metformin influences the cytophysiology of somatic cells in a dose- and time-dependent manner causing inhibition of proliferation and abnormalities of their morphology and ultrastructure.

2006 ◽  
Vol 141 (4) ◽  
pp. 530-535 ◽  
Author(s):  
N. S. Sergeeva ◽  
I. K. Sviridova ◽  
V. A. Kirsanova ◽  
S. A. Akhmedova ◽  
N. V. Marshutina ◽  
...  

Author(s):  
Dmitrijs Babarikins ◽  
Guntra Krūmiņa ◽  
Irina Paegle ◽  
Diāna Amerika ◽  
Zaiga Krūmiņa ◽  
...  

Red beetroot (Beta vulgaris) juice (RBJ) is used as a traditional medicine for treatment of anemia. It has been shown that beetroot juice decreases blood pressure, provides a protective effect on blood vessels and has antioxidant and anticancerogenic properties. In the case of polytrauma it might have beneficial effects because of its antioxidant and anti-inflammatory properties as well as antimicrobial activity. It is also well-known that RBR juice can induce undesirable side effects, e.g. flatulent stomach, nausea and other unpleasant reactions. Therefore, it seems prospective to develop red beetroot juice based on its natural compound composition free of undesirable side effects, which could then be used in combination with bone marrow multipotent mesenchymal stromal cells (BM MMSC) transplantation in the case of polytrauma. The aim of the study was to evaluate the therapeutic effect of allogeneic BM MMSC transplantation in rats with experimental polytrauma and to analyse red beetroot fractions separated on the basis of molecular weight in regard to their ingestion impact on cell transplantation efficacy. Red beet juice was fractionated by ultrafiltration (cut-off-point 20 kDa). Total phenolic compound concentration in the final product practically did not decrease. The product was tested in vitro and in vivo. Unlike native juice, fractionated RBJ in vitro suppressed BM MMSC adipogenic (60-71%, P < 0.05) and stimulated osteogenic differentiation (124%, P < 0.05). Experimental polytrauma in rats was modelled by causing three fractures and haemorrhagic shock. Animals were randomised in five groups: 1) normal control; 2) polytrauma; 3) polytrauma + i/v BM MMSC transplantation 36 h and 5 days after surgery; 4) polytrauma + fractionated RBJ administration per os 1ml/d, and 5) polytrauma + BM MMSCs + fractionated RBJ. Transplantation of allogeneic BM MMSCs in rats with experimental polytrauma stimulated bone fracture reparation, but caused plethora in viscera and dystrophic changes in lungs. Combination of BM MMSCs and fractionated RBJ resulted in better bone reparation and significant hematopoiesis stimulation.


2017 ◽  
Vol 5 (2) ◽  
pp. 194-199
Author(s):  
A. Rodnichenko

Multipotent mesenchymal stromal cells (MMSCs) are used for cell therapy of lesions of various genesis. The most widely used MMSCs are from two tissue sources: bone marrow and adipose tissue.The purpose of the work was to conduct a comparative assessment of the biological properties of murine bone marrow-derived and adipose tissue-derived MMSCs.Methods. The culture of MMSCs was obtained from the bone marrow and adipose tissue of 6 months-old male FVB/N mice according to standard protocols. We performed phenotyping, directed osteogenic and adipogenic differentiation, analysis of immunomodulatory properties in vitro of obtained cell cultures.Results. The cultured MMSCs from bone marrow and adipose tissue express the typical stromal markers (CD44, CD73, CD90 and Sca-1). A distinctive feature of bone marrow cells cultures of the 2nd passage was the high level of the hematopoietic markers CD45 and CD117 expression. MMSCs from both tissue sources are capable of differentiation in the osteogenic and adipogenic directions. At the same time, there were differences in the differentiation in the osteogenic direction – adipose tissue-derived MMSCs had a lower osteogenic potential. MMSCs exhibit inhibitory effect on mitogen-induced proliferation of splenocytes in vitro, expression of which does not depend on tissue origin of the MMSCs with significant inhibition of mitogen-induced proliferation of splenocytes at addition of high doses of MMSCs.Conclusions. MMSCs of bone marrow and adipose tissue express a similar level of surface markers that are characteristic of cells with multipotent properties. They are capable to differentiating in osteo- and adipogenic direction with differences in the degree of mineralization of the extracellular matrix and exhibit immunomodulatory effects in vitro, regardless of tissue origin.


Heliyon ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. e06517
Author(s):  
Lyudmila M. Mezhevikina ◽  
Dmitriy A. Reshetnikov ◽  
Maria G. Fomkina ◽  
Nurbol O. Appazov ◽  
Saltanat Zh. Ibadullayeva ◽  
...  

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 ◽  
...  

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.


2019 ◽  
Vol 60 (8) ◽  
pp. 2042-2049
Author(s):  
Irina N. Shipounova ◽  
Nataliya A. Petinati ◽  
Alexey E. Bigildeev ◽  
Tamara V. Sorokina ◽  
Larisa A. Kuzmina ◽  
...  

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 403
Author(s):  
Girolamo Di Maio ◽  
Nicola Alessio ◽  
Ibrahim Halil Demirsoy ◽  
Gianfranco Peluso ◽  
Silverio Perrotta ◽  
...  

Brown-like adipocytes can be induced in white fat depots by a different environmental or drug stimuli, known as “browning” or “beiging”. These brite adipocytes express thermogenin UCP1 protein and show different metabolic advantages, such as the ability to acquire a thermogenic phenotype corresponding to standard brown adipocytes that counteracts obesity. In this research, we evaluated the effects of several browning agents during white adipocyte differentiation of bone marrow-derived mesenchymal stromal cells (MSCs). Our in vitro findings identified two compounds that may warrant further in vivo investigation as possible anti-obesity drugs. We found that rosiglitazone and sildenafil are the most promising drug candidates for a browning treatment of obesity. These drugs are already available on the market for treating diabetes and erectile dysfunction, respectively. Thus, their off-label use may be contemplated, but it must be emphasized that some severe side effects are associated with use of these drugs.


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