scholarly journals Preclinical Evaluation of Sodium Selenite in Mice: Toxicological and Tumor Regression Studies after Striatum Implantation of Human Glioblastoma Stem Cells

2021 ◽  
Vol 22 (19) ◽  
pp. 10646
Author(s):  
Louis Larrouquère ◽  
Sylvie Berthier ◽  
Benoit Chovelon ◽  
Catherine Garrel ◽  
Véronique Vacchina ◽  
...  
Keyword(s):  
Stem Cells ◽  
Nude Mice ◽  
Sodium Selenite ◽  
Tumor Regression ◽  
Statistical Significance ◽  
Selenium Concentration ◽  
Preclinical Study ◽  
Control Group ◽  
New Treatments

Glioblastoma (GBM) is the most aggressive malignant glioma, with a very poor prognosis; as such, efforts to explore new treatments and GBM’s etiology are a priority. We previously described human GBM cells (R2J-GS) as exhibiting the properties of cancer stem cells (growing in serum-free medium and proliferating into nude mice when orthotopically grafted). Sodium selenite (SS)—an in vitro attractive agent for cancer therapy against GBM—was evaluated in R2J-GS cells. To go further, we launched a preclinical study: SS was given orally, in an escalation-dose study (2.25 to 10.125 mg/kg/day, 5 days on, 2 days off, and 5 days on), to evaluate (1) the absorption of selenium in plasma and organs (brain, kidney, liver, and lung) and (2) the SS toxicity. A 6.75 mg/kg SS dose was chosen to perform a tumor regression assay, followed by MRI, in R2J-GS cells orthotopically implanted in nude mice, as this dose was nontoxic and increased brain selenium concentration. A group receiving TMZ (5 mg/kg) was led in parallel. Although not reaching statistical significance, the group of mice treated with SS showed a slower tumor growth vs. the control group (p = 0.08). No difference was observed between the TMZ and control groups. We provide new insights of the mechanisms of SS and its possible use in chemotherapy.

scholarly journals Ionizing radiation augments glioma tropism of mesenchymal stem cells

2018 ◽  
Vol 128 (1) ◽  
pp. 287-295 ◽  
Author(s):  
Jonathan G. Thomas ◽  
Brittany C. Parker Kerrigan ◽  
Anwar Hossain ◽  
Joy Gumin ◽  
Naoki Shinojima ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ionizing Radiation ◽  
Nude Mice ◽  
Tissue Injury ◽  
Statistical Significance ◽  
Dependent Manner ◽  
Weak Attractor ◽  
Dose Dependent

OBJECTIVEMesenchymal stem cells (MSCs) have been shown to localize to gliomas after intravascular delivery. Because these cells home to areas of tissue injury, the authors hypothesized that the administration of ionizing radiation (IR) to tumor would enhance the tropism of MSCs to gliomas. Additionally, they sought to identify which radiation-induced factors might attract MSCs.METHODSTo assess the effect of IR on MSC migration in vitro, transwell assays using conditioned medium (CM) from an irradiated commercially available glioma cell line (U87) and from irradiated patient-derived glioma stem-like cells (GSCs; GSC7-2 and GSC11) were employed. For in vivo testing, green fluorescent protein (GFP)-labeled MSCs were injected into the carotid artery of nude mice harboring orthotopic U87, GSC7-2, or GSC17 xenografts that were treated with either 0 or 10 Gy of IR, and brain sections were quantitatively analyzed by immunofluorescence for GFP-positive cells. These GSCs were used because GSC7-2 is a weak attractor of MSCs at baseline, whereas GSC17 is a strong attractor. To determine the factors implicated in IR-induced tropism, CM from irradiated GSC7-2 and from GSC11 was assayed with a cytokine array and quantitative ELISA.RESULTSTranswell migration assays revealed statistically significant enhanced MSC migration to CM from irradiated U87, GSC7-2, and GSC11 compared with nonirradiated controls and in a dose-dependent manner. After their intravascular delivery into nude mice harboring orthotopic gliomas, MSCs engrafted more successfully in irradiated U87 (p = 0.036), compared with nonirradiated controls. IR also significantly increased the tropism of MSCs to GSC7-2 xenografts (p = 0.043), which are known to attract MSCs only poorly at baseline (weak-attractor GSCs). Ionizing radiation also increased the engraftment of MSCs in strong-attractor GSC17 xenografts, but these increases did not reach statistical significance. The chemokine CCL2 was released by GSC7-2 and GSC11 after irradiation in a dose-dependent manner and mediated in vitro transwell migration of MSCs. Immunohistochemistry revealed increased CCL2 in irradiated GSC7-2 gliomas near the site of MSC engraftment.CONCLUSIONSAdministering IR to gliomas enhances MSC localization, particularly in GSCs that attract MSCs poorly at baseline. The chemokine CCL2 appears to play a crucial role in the IR-induced tropism of MSCs to gliomas.

scholarly journals Bone Regeneration by Nanohydroxyapatite/Chitosan/Poly(lactide-co-glycolide) Scaffolds Seeded with Human Umbilical Cord Mesenchymal Stem Cells in the Calvarial Defects of the Nude Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Fei Wang ◽  
Xiao-Xia Su ◽  
Yu-Cheng Guo ◽  
Ang Li ◽  
Yin-Cheng Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Regeneration ◽  
Umbilical Cord ◽  
Nude Mice ◽  
Fluorescence Labeling ◽  
Control Group ◽  
Human Umbilical Cord ◽  
Calvarial Defects

In the preliminary study, we have found an excellent osteogenic property of nanohydroxyapatite/chitosan/poly(lactide-co-glycolide) (nHA/CS/PLGA) scaffolds seeded with human umbilical cord mesenchymal stem cells (hUCMSCs)in vitroand subcutaneously in the nude mice. The aim of this study was to further evaluate the osteogenic capacity of nHA/CS/PLGA scaffolds seeded with hUCMSCs in the calvarial defects of the nude mice. Totally 108 nude mice were included and divided into 6 groups: PLGA scaffolds + hUCMSCs; nHA/PLGA scaffolds + hUCMSCs; CS/PLGA scaffolds + hUCMSCs; nHA/CS/PLGA scaffolds + hUCMSCs; nHA/CS/PLGA scaffolds without seeding; the control group (no scaffolds) (n=18). The scaffolds were implanted into the calvarial defects of nude mice. The amount of new bones was evaluated by fluorescence labeling, H&E staining, and Van Gieson staining at 4 and 8 weeks, respectively. The results demonstrated that the amount of new bones was significantly increased in the group of nHA/CS/PLGA scaffolds seeded with hUCMSCs (p<0.01). On the basis of previous studiesin vitroand in subcutaneous implantation of the nude mice, the results revealed that the nHA and CS also enhanced the bone regeneration by nHA/CS/PLGA scaffolds seeded with hUCMSCs in the calvarial defects of the nude mice at early stage.

scholarly journals Combination of umbilical cord mesenchymal stem cells and standard immunosuppressive regimen for pediatric patients with severe aplastic anemia

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yang Lan ◽  
Fang Liu ◽  
Lixian Chang ◽  
Lipeng Liu ◽  
Yingchi Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Aplastic Anemia ◽  
Umbilical Cord ◽  
Pediatric Patients ◽  
Statistical Significance ◽  
Severe Aplastic Anemia ◽  
Control Group ◽  
Open Label ◽  
Cell Counts

Abstract Background Defects of bone marrow mesenchymal stem cells (BM-MSCs) in proliferation and differentiation are involved in the pathophysiology of aplastic anemia (AA). Infusion of umbilical cord mesenchymal stem cells (UC-MSCs) may improve the efficacy of immunosuppressive therapy (IST) in childhood severe aplastic anemia (SAA). Methods We conducted an investigator-initiated, open-label, and prospective phase IV trial to evaluate the safety and efficacy of combination of allogenic UC-MSCs and standard IST for pediatric patients with newly diagnosed SAA. In mesenchymal stem cells (MSC) group, UC-MSCs were injected intravenously at a dose of 1 × 106/kg per week starting on the 14th day after administration of rabbit antithymocyte globulin (ATG), for a total of 3 weeks. The clinical outcomes and adverse events of patients with UC-MSCs infusion were assessed when compared with a concurrent control group in which patients received standard IST alone. Results Nine patients with a median age of 4 years were enrolled as the group with MSC, while the data of another 9 childhood SAA were analysed as the controls. Four (44%) patients in MSC group developed anaphylactic reactions which were associated with rabbit ATG. When compared with the controls, neither the improvement of blood cell counts, nor the change of T-lymphocytes after IST reached statistical significance in MSC group (both p > 0.05) and there were one (11%) patient in MSC group and two (22%) patients in the controls achieved partial response (PR) at 90 days after IST. After a median follow-up of 48 months, there was no clone evolution occurring in both groups. The 4-year estimated overall survival (OS) rate in two groups were both 88.9% ± 10.5%, while the 4-year estimated failure-free survival (FFS) rate in MSC group was lower than that in the controls (38.1% ± 17.2% vs. 66.7% ± 15.7%, p = 0.153). Conclusions Concomitant use of IST and UC-MSCs in SAA children is safe but may not necessarily improve the early response rate and long-term outcomes. This clinical trial was registered at ClinicalTrials.gov, identifier: NCT02218437 (registered October 2013).

scholarly journals Effects of Naringin on Proliferation and Osteogenic Differentiation of Human Periodontal Ligament Stem Cells In Vitro and In Vivo

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Lihua Yin ◽  
Wenxiao Cheng ◽  
Zishun Qin ◽  
Hongdou Yu ◽  
Zhanhai Yu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Osteogenic Differentiation ◽  
Periodontal Ligament ◽  
Trabecular Structure ◽  
Control Group ◽  
Periodontal Ligament Stem Cells ◽  
Expression Levels ◽  
Proliferation And Differentiation

This study is to explore the osteogenesis potential of the human periodontal ligament stem cells (hPDLSCs) induced by naringin in vitro and in vitro. The results confirmed that 1 μM naringin performs the best effect and a collection of bone-related genes (RUNX2,COL1A2, OPN, and OCN) had significantly higher expression levels compared to the control group. Furthermore, a typical trabecular structure was observed in vivo, surrounded by a large amount of osteoblasts. These results demonstrated that naringin, at a concentration of 1 μM, can efficiently promote the proliferation and differentiation of hPDLSCs both in vitro and in vivo.

scholarly journals A New Patient-Derived Metastatic Glioblastoma Cell Line: Characterisation and Response to Sodium Selenite Anticancer Agent

Cancers ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 12 ◽  
Author(s):  
Sylvie Berthier ◽  
Louis Larrouquère ◽  
Pierre Champelovier ◽  
Edwige Col ◽  
Christine Lefebvre ◽  
...  
Keyword(s):  
Cell Line ◽  
Sodium Selenite ◽  
Leptomeningeal Metastasis ◽  
Therapeutic Window ◽  
Patient Specific ◽  
Histone 3 ◽  
Anticancer Effects ◽  
Human Gbm ◽  
New Treatments

Glioblastoma multiform (GBM) tumors are very heterogeneous, organized in a hierarchical pattern, including cancer stem cells (CSC), and are responsible for development, maintenance, and cancer relapse. Therefore, it is relevant to establish new GBM cell lines with CSC characteristics to develop new treatments. A new human GBM cell line, named R2J, was established from the cerebro-spinal fluid (CSF) of a patient affected by GBM with leptomeningeal metastasis. R2J cells exhibits an abnormal karyotype and form self-renewable spheres in a serum-free medium. Original tumor, R2J, cultured in monolayer (2D) and in spheres showed a persistence expression of CD44, CD56 (except in monolayer), EGFR, Ki67, Nestin, and vimentin. The R2J cell line is tumorigenic and possesses CSC properties. We tested in vitro the anticancer effects of sodium selenite (SS) compared to temozolomide TMZ. SS was absorbed by R2J cells, was cytotoxic, induced an oxidative stress, and arrested cell growth in G2M before inducing both necrosis and apoptosis via caspase-3. SS also modified dimethyl-histone-3-lysine-9 (H3K9m2) levels and decreased histone deacetylase (HDAC) activity, suggesting anti-invasiveness potential. This study highlights the value of this new GBM cell line for preclinical modeling of clinically relevant, patient specific GBM and opens a therapeutic window to test SS to target resistant and recurrent GBM.

scholarly journals Comparison of biotechnological culture of hypoxia-conditioned rat mesenchymal stem cells with conventional in vitro culture of normoxia-conditioned rat mesenchymal stem cells for testicular failure therapy with low libido in rats

2019 ◽  
Vol 12 (6) ◽  
pp. 916-924 ◽  
Author(s):  
Erma Safitri ◽  
Mas'ud Hariadi
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Functional Outcome ◽  
Leydig Cells ◽  
Control Group ◽  
Spermatogenic Cells ◽  
Hematopoietic Stem ◽  
T1 And T2 ◽  
Testicular Failure

Aim: Biotechnological culture of hypoxia-conditioned (CH) rat mesenchymal stem cells (rMSC-CH) for testicular failure therapy with low libido improves the functional outcome of the testicle for producing spermatogenic cells and repairs Leydig cells in rats (Rattus norvegicus). Materials and Methods: In the first group (T1), rats with testicular failure and low libido were injected with normoxia-conditioned (CN) rMSCs (21% oxygen); in the second group (T2), rats with testicular failure and low libido were injected with rMSC-CH (1% oxygen); in the negative control group (T–), rats with normal testis were injected with 0.1 mL phosphate-buffered saline (PBS); and in the sham group (TS), rats with testicular failure and low libido were injected with 0.1 mL of PBS. Results: Vascular endothelial growth factor expression, as the homing signal, in the groups T2, T–, T1, and TS was 2.00±0.5%, 2.95±0.4%, 0.33±0.48%, and 0±0%, respectively. The number of cluster of differentiation (CD)34+ and CD45+ cells in the groups T– and TS was <20%, whereas that in T1 and T2 groups was >30% and >80%, respectively, showing the mobilization of hematopoietic stem cells (HSCs). The number of spermatogenic cells (spermatogonia, primary spermatocytes, secondary spermatocytes, and spermatid) decreased significantly (p<0.05) in TS compared with that in T–, T1, and T2, whereas that in T2 did not show a significant (p>0.05) decrease compared to that in T–. The improvement in libido, based on the number of Leydig cells producing the hormone testosterone for libido expression, did not increase in T1, whereas T2 was able to maintain the number of Leydig cells significantly compared to that between TS and T1. Conclusion: rMSC-CH culture for testicular failure with low libido showed improvement in the functional outcome of the testicle and in repairing Leydig cells.

scholarly journals Human menstrual blood-derived stem cells mitigate bleomycin-induced pulmonary fibrosis through anti-apoptosis and anti-inflammatory effects

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xin Chen ◽  
Yi Wu ◽  
Yanling Wang ◽  
Lijun Chen ◽  
Wendi Zheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pulmonary Fibrosis ◽  
Therapeutic Potential ◽  
Lung Fibroblasts ◽  
Menstrual Blood ◽  
Inflammatory Factors ◽  
Mouse Lung ◽  
Control Group ◽  
Antibody Array

Abstract Background Idiopathic pulmonary fibrosis is a kind of diffuse interstitial lung disease, the pathogenesis of which is unclear, and there is currently a lack of good treatment to improve the survival rate. Human menstrual blood-derived mesenchymal stem cells (MenSCs) have shown great potential in regenerative medicine. This study aimed to explore the therapeutic potential of MenSCs for bleomycin-induced pulmonary fibrosis. Methods We investigated the transplantation of MenSCs in a pulmonary fibrosis mouse model induced by BLM. Mouse was divided into three groups: control group, BLM group, MenSC group. Twenty-one days after MenSC transplantation, we examined collagen content, pathological, fibrosis area in the lung tissue, and the level of inflammatory factors of serum. RNA sequence was used to examine the differential expressed gene between three groups. Transwell coculture experiments were further used to examine the function of MenSCs to MLE-12 cells and mouse lung fibroblasts (MLFs) in vitro. Results We observed that transplantation of MenSCs significantly improves pulmonary fibrosis mouse through evaluations of pathological lesions, collagen deposition, and inflammation. Transwell coculturing experiments showed that MenSCs suppress the proliferation and the differentiation of MLFs and inhibit the apoptosis of MLE-12 cells. Furthermore, antibody array results demonstrated that MenSCs inhibit the apoptosis of MLE-12 cells by suppressing the expression of inflammatory-related cytokines, including RANTES, Eotaxin, GM-CSF, MIP-1γ, MCP-5, CCL1, and GITR. Conclusions Collectively, our results suggested MenSCs have a great potential in the treatment of pulmonary fibrosis, and cytokines revealed in antibody array are expected to become the target of future therapy of MenSCs in clinical treatment of pulmonary fibrosis.

The first trimester aneuploidy biochemical markers in IVF/ICSI patients have no additional benefit compared to spontaneous conceptions in the prediction of pregnancy complications

2018 ◽  
Vol 46 (9) ◽  
pp. 953-959
Author(s):  
Iwona Szymusik ◽  
Przemyslaw Kosinski ◽  
Katarzyna Kosinska-Kaczynska ◽  
Damian Warzecha ◽  
Anetta Karwacka ◽  
...  
Keyword(s):  
Pregnancy Complications ◽  
Biochemical Markers ◽  
Gestational Hypertension ◽  
Statistical Significance ◽  
Protein A ◽  
First Trimester ◽  
Serum Markers ◽  
Control Group ◽  
Assisted Reproduction Technique

AbstractObjectives:The aim of this study was to determine if the levels of biochemical aneuploidy markers inin vitrofertilisation (IVF)/intracytoplasmic sperm injection (ICSI) pregnancies differ from those in spontaneous pregnancies and to verify if biochemical markers could predict pregnancy outcome in IVF/ICSI gestations.Methods:This was a prospective observational study performed in a group of 551 patients who underwent a combined first trimester prenatal screening (ultrasound scan and serum markers). All patients were divided into two groups according to the mode of conception: IVF/ICSI pregnancies (study group) and spontaneous conceptions (control group). The concentrations of first trimester biochemical markers were presented as multiples of median (MoM) and were compared between the study and control groups. Analysed pregnancy complications included: preterm delivery (PTD), small for gestational age (SGA), gestational hypertension (GH), preeclampsia (PE) and gestational diabetes (GDM).Results:The analysis was performed on 183 IVF/ICSI and 368 spontaneously conceived gestations, with complete data regarding obstetric outcome. There were no significant differences in the concentrations of biochemical markers between the analysed groups. Pregnancy-associated plasma protein-A (PAPP-A) levels were lower in hypertensive than in normotensive patients, although the difference was not significant. Twenty-three patients had GDM (12.5%), 16 had GH or PE (8.7%), SGA was diagnosed in 18 (9.8%) and 25 delivered preterm (13.6%).Conclusions:The trend for lower PAPP-A MoM was visible in all affected patients, although the results did not reach statistical significance. The first trimester biochemical markers in assisted reproduction technique (ART) pregnancies do not seem to have additional effect on predicting the risk of pregnancy complications.

scholarly journals Effect of a long-term peroral supplementation with sodium selenite and selenium lactate-protein complex on selenium status in goats and their kids

2009 ◽  
Vol 54 (No. 7) ◽  
pp. 324-332 ◽  
Author(s):  
L. Misurova ◽  
L. Pavlata ◽  
A. Pechova ◽  
R. Dvorak
Keyword(s):  
Glutathione Peroxidase ◽  
Protein Complex ◽  
Sodium Selenite ◽  
Selenium Concentration ◽  
Selenium Supplementation ◽  
Control Group ◽  
Glutathione Peroxidase Activity ◽  
Significant Difference ◽  
Average Activity

The aim of this study was to evaluate the effect of a long-term peroral selenium supplementation in the form of sodium selenite and selenium lactate-protein complex by comparing selenium concentrations and glutathione peroxidase activity in blood of goats and their kids as well as comparing selenium concentrations in goat colostrums. For the study, a total of 27 clinically healthy pregnant white shorthair goats were used. They were divided to three groups, i.e., the control group (C) without any selenium supplementation, sodium selenite group (E1) and selenium lactate-protein complex group (E2). For four months, experimental goats received 0.43 mg of selenium per animal per day in diet; goats from the control group were given 0.15 mg of selenium per animal per day. At the beginning of the experiment, goats of all groups showed an average selenium concentration of 96 &mu;g/l in whole blood. On the parturition day, samples of first colostrum from goats and heparinized blood from goats and kids were taken. In the control group (C), average blood selenium concentrations of 111.4 ± 33.5 &mu;g/l were observed on the parturition day. In both experimental groups, selenium concentrations were significantly higher (<I>P</I> < 0.05). Average selenium concentration in the sodium selenite group (E1) was 177.2 ± 34.8 &mu;g/l and in the group supplemented with selenium lactate-protein complex (E2) 159.0 ± 28.5 &mu;g/l. Average glutathione peroxidase (GSH-Px) activity in blood of control goats (C) was 581.9 ± 99.2 &mu;kat/l, in group E1 1 154.6 ± 156.2 &mu;kat/l and in group E2 1 011.6 ± 153.6 &mu;kat/l. GSH-Px activity in experimental groups was significantly higher (<I>P</I> < 0.05) as compared with the control group. Average selenium concentrations in colostrum was in the control group 40.1 ± 12.8 &mu;g/l, in E1 99.0 ± 29.9 &mu;g/l and in group E2 79.0 ± 17.7 &mu;g/l. Colostral selenium concentrations in experimental groups were significantly higher (<I>P</I> < 0.05) as compared with the control group. No significant difference in the monitored parameters was found between experimental groups. In kids of control mothers (kC), average selenium concentrations in blood on the parturition day were 62.4 ± 22.9 &mu;g/l; kids of mothers supplemented with sodium selenite (kE1) showed average selenium levels of 100.0 ± 31.2 &mu;g/l, and the average selenium concentration in kids of mothers receiving lactate-protein complex was 83.4 ± 20.1 &mu;g/l (kE2). Average GSH-Px activity in control kids (kC) was 402.1 ± 153.9 &mu;kat/l. Kids from kE1 showed average activity of GSH-Px 806.1 ± 254.9 &mu;kat/l and kids from group kE2 529.9 ± 119.8 &mu;kat/l. Statistically significant difference (<I>P</I> < 0.05) was found only between kC and kE1 which showed significantly higher selenium concentration and GSH-Px activity. The results of this study confirm that both forms of selenium administered in experimental groups (i.e., sodium selenite and selenium lactate-protein complex) had similar biological effect in goats. However, results obtained in kids indicate a better effect of supplementation with sodium selenite.

Abstract 4759: Integrated in vitro and in vivo screening of tumor and normal neural stem cells identifies potential new treatments of ependymoma

2011 ◽  
Author(s):  
Jennifer M. Atkinson ◽  
Anang A. Shelat ◽  
Tanya A. Kranenburg ◽  
Angel M. Carcaboso ◽  
Alexander Arnold ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
In Vivo Screening ◽  
New Treatments
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