scholarly journals The effects of different doses of thymulin in vivo and in vitro on some biological properties of bone marrow-derived multipotent mesenchymal stromal cells in mice of different strains

2018 ◽  
Vol 6 (1) ◽  
pp. 66-73
Author(s):  
I. Labunets ◽  
◽  
A. Rodnichenko ◽  
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.


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.


2018 ◽  
Vol 205 (4) ◽  
pp. 226-239 ◽  
Author(s):  
Marijana Skific ◽  
Mirna Golemovic ◽  
Kristina Crkvenac-Gornik ◽  
Radovan Vrhovac ◽  
Branka Golubic Cepulic

Due to their ability to induce immunological tolerance in the recipient, mesenchymal stromal cells (MSCs) have been utilized in the treatment of various hematological and immune- and inflammation-mediated diseases. The clinical application of MSCs implies prior in vitro expansion that usually includes the use of fetal bovine serum (FBS). The present study evaluated the effect of different platelet lysate (PL) media content on the biological properties of MSCs. MSCs were isolated from the bone marrow of 13 healthy individuals and subsequently expanded in three different culture conditions (10% PL, 5% PL, 10% FBS) during 4 passages. The cells cultured in different conditions had comparable immunophenotype, clonogenic potential, and differentiation capacity. However, MSC growth was significantly enhanced in the presence of PL. Cultures supplemented with 10% PL had a higher number of cumulative population doublings in all passages when compared to the 5% PL condition (p < 0.03). Such a difference was also observed when 10% PL and 10% FBS conditions were compared (p < 0.005). A statistically significant difference in population doubling time was determined only between the 10% PL and 10% FBS conditions (p < 0.005). Furthermore, MSCs cultured in 10% PL were able to cause a 66.9% reduction of mitogen-induced lymphocyte proliferation. Three chromosome aberrations were detected in PL conditions. Since two changes occurred in the same do nor, it is possible they were donor dependent rather than caused by the culture condition. These findings demonstrate that a 10% PL condition enables a higher yield of MSCs within a shorter time without altering MSC properties, and should be favored over the 5% PL condition.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Xiaolei Huang ◽  
Yang Xue ◽  
Jinliang Wu ◽  
Qing Zhan ◽  
Jiangmin Zhao

We aimed to identify a suitable method for long-term monitoring of the migration and proliferation of mesenchymal stromal cells in stroke models of rats using ferritin transgene expression by magnetic resonance imaging (MRI). Bone marrow mesenchymal stromal cells (BMSCs) were transduced with a lentivirus containing a shuttle plasmid (pCDH-CMV-MCS-EF1-copGFP) carrying the ferritin heavy chain 1 (Fth1) gene. Ferritin expression in stromal cells was evaluated with western blotting and immunofluorescent staining. The iron uptake of Fth1-BMSCs was measured with Prussian blue staining. Following surgical introduction of middle cerebral artery occlusion, Fth1-BMSCs and superparamagnetic iron oxide- (SPIO-) labeled BMSCs were injected through the internal jugular vein. The imaging and signal intensities were monitored by diffusion-weighted imaging (DWI), T2-weighted imaging (T2WI), and susceptibility-weighted imaging (SWI) in vitro and in vivo. Pathology was performed for comparison. We observed that the MRI signal intensity of SPIO-BMSCs gradually reduced over time. Fth1-BMSCs showed the same signal intensity between 10 and 60 days. SWI showed hypointense lesions in the SPIO-BMSC (traceable for 30 d) and Fth1-BMSC groups. T2WI was not sensitive enough to trace Fth1-BMSCs. After transplantation, Prussian blue-stained cells were observed around the infarction area and in the infarction center in both transplantation models. Fth1-BMSCs transplanted for treating focal cerebral infarction were safe, reliable, and traceable by MRI. Fth1 labeling was more stable and suitable than SPIO labeling for long-term tracking. SWI was more sensitive than T2W1 and suitable as the optimal MRI-tracking sequence.


2019 ◽  
Vol 20 (15) ◽  
pp. 3639 ◽  
Author(s):  
Giorgia Maroni ◽  
Daniele Panetta ◽  
Raffaele Luongo ◽  
Indira Krishnan ◽  
Federica La Rosa ◽  
...  

Molecular mechanisms governing cell fate decision events in bone marrow mesenchymal stromal cells (MSC) are still poorly understood. Herein, we investigated the homeobox gene Prep1 as a candidate regulatory molecule, by adopting Prep1 hypomorphic mice as a model to investigate the effects of Prep1 downregulation, using in vitro and in vivo assays, including the innovative single cell RNA sequencing technology. Taken together, our findings indicate that low levels of Prep1 are associated to enhanced adipogenesis and a concomitant reduced osteogenesis in the bone marrow, suggesting Prep1 as a potential regulator of the adipo-osteogenic differentiation of mesenchymal stromal cells. Furthermore, our data suggest that in vivo decreased Prep1 gene dosage favors a pro-adipogenic phenotype and induces a “browning” effect in all fat tissues.


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

2015 ◽  
Vol 13 ◽  
pp. 254-265 ◽  
Author(s):  
Wanxun Yang ◽  
Sanne K. Both ◽  
Gerjo J.V.M. van Osch ◽  
Yining Wang ◽  
John A. Jansen ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Per Anderson ◽  
Elena Gonzalez-Rey ◽  
Francisco O’Valle ◽  
Francisco Martin ◽  
F. Javier Oliver ◽  
...  

Multipotent mesenchymal stromal cells (MSCs) have emerged as a promising therapy for autoimmune diseases, including multiple sclerosis (MS). Administration of MSCs to MS patients has proven safe with signs of immunomodulation but their therapeutic efficacy remains low. The aim of the current study has been to further characterize the immunomodulatory mechanisms of adipose tissue-derived MSCs (ASCs) in vitro and in vivo using the EAE model of chronic brain inflammation in mice. We found that murine ASCs (mASCs) suppress T cell proliferation in vitro via inducible nitric oxide synthase (iNOS) and cyclooxygenase- (COX-) 1/2 activities. mASCs also prevented the lipopolysaccharide- (LPS-) induced maturation of dendritic cells (DCs) in vitro. The addition of the COX-1/2 inhibitor indomethacin, but not the iNOS inhibitor L-NAME, reversed the block in DC maturation implicating prostaglandin (PG) E2 in this process. In vivo, early administration of murine and human ASCs (hASCs) ameliorated myelin oligodendrocyte protein- (MOG35-55-) induced EAE in C57Bl/6 mice. Mechanistic studies showed that mASCs suppressed the function of autoantigen-specific T cells and also decreased the frequency of activated (CD11c+CD40high and CD11c+TNF-α+) DCs in draining lymph nodes (DLNs). In summary, these data suggest that mASCs reduce EAE severity, in part, through the impairment of DC and T cell function.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Hongyu Qiao ◽  
Ran Zhang ◽  
Lina Gao ◽  
Yanjie Guo ◽  
Jinda Wang ◽  
...  

Introduction. Bone marrow-derived mesenchymal stromal cells (BMSCs) have emerged as promising cell candidates but with poor survival after transplantation. This study was designed to investigate the efficacy of VEGF, bFGF, and IGF-1 on BMSCs’ viability and proliferation bothin vivoandin vitrousing bioluminescence imaging (BLI).Methods. BMSCs were isolated fromβ-actin-Fluc+transgenic FVB mice, which constitutively express firefly luciferase. Apoptosis was induced by hypoxia preconditioning for up to 24 h followed by flow cytometry and TUNEL assay. 106BMSCs with/without growth factors were injected subcutaneously into wild type FVB mice’s backs. Survival of BMSCs was longitudinally monitored using bioluminescence imaging (BLI) for 5 weeks. Protein expression of Akt, p-Akt, PARP, and caspase-3 was detected by Western blot.Results. Hypoxia-induced apoptosis was significantly attenuated by bFGF and IGF-1 compared with VEGF and control groupin vitro(P<0.05). When combined with matrigel, IGF-1 showed the most beneficial effects in protecting BMSCs from apoptosisin vivo.The phosphorylation of Akt had a higher ratio in the cells from IGF-1 group.Conclusion. IGF-1 could protect BMSCs from hypoxia-induced apoptosis through activation of p-Akt/Akt pathway.


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