scholarly journals Bone marrow mesenchymal stem cell co-adjuvant therapy with albendazole for managing Toxocara vitulorum-rat model

2021 ◽  
Vol 14 (2) ◽  
pp. 347-363
Author(s):  
Faten A. M. Abo-Aziza ◽  
Abdel Kader A. Zaki ◽  
Ahmed I. Alajaji ◽  
Saleh M. Al barrak
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Liver Enzymes ◽  
Therapeutic Potential ◽  
Flow Cytometric Analysis ◽  
Phagocytic Index ◽  
Hepatic Tissue ◽  
Histopathological Findings ◽  
Toxocara Vitulorum ◽  
Tnf Α

Background and Aim: Toxocara vitulorum is a bovine intestinal nematode. Immune pictures following infection are conflicting and stopping anthelmintic albendazole treatment recording reversed liver abnormalities. The purpose of this work was to evaluate the therapeutic potential of bone marrow mesenchymal stem cells (BMMSCs) therapy, subsequent to albendazole administration in rats infected with T. vitulorum. Materials and Methods: The ultrasonographic and histopathological examinations as well as serum liver enzymes activity and the kinetics of recovery were investigated. The correlation of cell-mediated and humoral immune pictures was assessed by assaying immunoglobulins, splenocytes viability, phagocytic index, and Th1/Th2 cytokines. Results: The cultured BMMSCs counting were 4.21×104 cells/cm2 with 96.03% viability. Flow-cytometric analysis indicated positive CD90 (82%), CD105 (79%) and negative CD34 (0.37%), CD45 (0.42%), attesting to the suitability of the isolated BMMSCs for use in therapy. Transplantation of BMMSCs after albendazole administration significantly reduced the release of liver enzymes (p<0.05) indicating liver cellularity improvement. The ultrasonographic, macroscopic, and histopathological findings confirmed the biochemical results. Significant elevation in the levels of tumor necrosis factor (TNF)-α and interferon (INF)-γ with a decline in interleukin (IL)-4 was observed in the untreated model (p<0.05). However, albendazole treatment followed by BMMSCs therapy significantly lowered the release of TNF-α and INF-γ, associated with significant production of IL-4 and IL-10 (p<0.05). Conclusion: The final results indicated that the liver functions, histopathological findings, and immune parameters were aggravated after experimental T. vitulorum infection. Albendazole treatment followed by BMMSCs therapy was found to assist in regeneration of injured hepatic tissue. Besides, it appeared to modulate host defensive immune responses against T. vitulorum antigens. This work could define more clearly the events that manipulate the host immune, histopathological, and biochemical responses to minimize obstacles in using stem cell therapy in animal toxocariosis.

scholarly journals Analysis of Bone Marrow-derived Mesenchymal Stem Cell Kinetics after Short-term Stimulation with Tumor Necrosis Factor-α (TNF-α)

2019 ◽  
Vol 28 (2) ◽  
pp. 99-108 ◽  
Author(s):  
Mio Naritani ◽  
Miho Inoue ◽  
Resmi Raju ◽  
Mayu Miyagi ◽  
Masamitsu Oshima ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Cell Kinetics ◽  
Short Term ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals NG2 as an Identity and Quality Marker of Mesenchymal Stem Cell Extracellular Vesicles

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1524 ◽  
Author(s):  
Mario Barilani ◽  
Valeria Peli ◽  
Alessandro Cherubini ◽  
Marta Dossena ◽  
Vincenza Dolo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cord Blood ◽  
Extracellular Vesicles ◽  
Therapeutic Potential ◽  
Antigen Expression ◽  
Quality Parameter ◽  
Proliferative Effect ◽  
Quality Marker

The therapeutic potential of mesenchymal stem cell (MSC) extracellular vesicles (EV) is currently under investigation in many pathological contexts. Both adult and perinatal MSC are being considered as sources of EV. Herein, we address antigen expression of cord blood and bone marrow MSC and released EV to define an identity and quality parameter of MSC EV as a medicinal product in the context of clinical applications. The research focuses on EV-shuttled neural/glial antigen 2 (NG2), which has previously been detected as a promising surface marker to distinguish perinatal versus adult MSC. Indeed, NG2 was significantly more abundant in cord blood than bone marrow MSC and MSC EV. Ultracentrifuge-isolated EV were then challenged for their pro-angiogenic properties on an xCELLigence system as quality control. NG2+ cord blood MSC EV, but not bone marrow MSC EV, promote bFGF and PDGF-AA proliferative effect on endothelial cells. Likewise, they successfully rescue angiostatin-induced endothelial cell growth arrest. In both cases, the effects are NG2-dependent. These results point at NG2 as an identity and quality parameter for cord blood MSC EV, paving the way for their clinical translation.

Leukemia-Induced Alterations in Bone Marrow Cytokine and Chemokine Levels Contribute to Altered Stem Cell Lodgment and Impairment of Normal Stem Cell Growth in CML

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 962-962
Author(s):  
Bin Zhang ◽  
Yin Wei Ho ◽  
Tessa L. Holyoake ◽  
Claudia S Huettner ◽  
Ravi Bhatia
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Mouse Model ◽  
Hematopoietic Stem Cell ◽  
Stromal Cells ◽  
Research Funding ◽  
Mrna Levels ◽  
Hematopoietic Stem ◽  
Tnf Α ◽  
Selective Impairment

Abstract Abstract 962 Specialized bone marrow (BM) microenvironmental niches are essential for hematopoietic stem cell (HSC) lodgment and maintenance. However microenvironmental interactions of leukemia stem cells (LSC) are poorly understood. Although chronic myelogenous leukemia (CML) results from HSC transformation by the BCR-ABL gene, the role of the microenvironment in modulating leukemia development is not known. We employed the SCL-tTA-BCR/ABL mouse model of CML to investigate the LSC interactions with the BM microenvironment. In this model, targeted expression of the BCR-ABL gene in murine HSC via a tet-regulated SCL promoter results in development of a chronic phase CML-like disorder. We have reported that LSC capacity is restricted to BCR-ABL+ cells with long-term hematopoietic stem cell (LTHSC) phenotype(LSK Flt3-CD150+CD48-) (Blood 2010 116:1212A). LSC numbers are reduced in the BM but increased in the spleen of CML mice compared with LTHSC from control mice, suggesting that LSC have altered niche interactions. LSC also demonstrate altered trafficking with significant reduction in homing of IV injected LSC to BM, and markedly increased egress of intrafemorally injected LSC to the spleen, potentially related to reduced CXCL12 levels in the BM of CML mice. In addition, levels of several chemokines and cytokines, including MIP1α, MIP1β, MIP2, IL-1α, IL-1β, TNF-α, G-CSF and IL-6, were increased in CML BM, related to increased production by malignant hematopoietic cells. We investigated whether altered chemokine and cytokine expression was associated with altered capacity of the CML BM microenvironment to support LTHSC engraftment. LTHSC from control mice or LSC from CML mice were transplanted into irradiated CML or control recipients. There was reduced engraftment of both control LTHSC and CML LSC in the BM of CML compared to control recipients at 2 weeks after transplantation, associated with reduced homing to CML BM, potentially related to low BM CXCL12 levels. The numbers of control LTHSC in the BM of CML recipient mice remained low at 4 weeks post-transplantation, whereas the numbers of CML LSC increased to numbers similar to those seen in the BM of control recipients. Culture with CML BM supernatants (SN) resulted in impaired growth of control LTHSC compared to control BM SN. In contrast the growth of CML LSC was similar following culture with CML and control BM SN. Culture with individual factors at concentrations similar to those observed in CML BM (16ng/ml MIP1α, 8ng/ml MIP1β, 2.5ng/ml IL-1α, 3.5ng/ml IL-1β, 0.05ng/ml TNF-α) resulted in significantly reduced growth of normal LTHSC compared with CML LSC. These results indicate that diffusible factors produced by leukemic cells in the CML BM environment selectively inhibit normal LTHSC compared to CML LSC growth. Exposure of a murine stromal cell line to CML BM SN resulted in reduced CXCL12 mRNA levels compared to BM SN from control mice. The cytokine G-CSF, which was increased in CML BM SN, has been reported to reduce CXCL12 transcription. We observed significant reduction of CXCL12 mRNA levels in stromal cells cultured with G-CSF (0.2ng/ml), supporting a potential role for increased G-CSF production by leukemia cells in reduced CXCL12 production by CML BM stromal cells and reduced LSC retention in the BM. We evaluated whether defects in microenvironmental function in CML were affected by imatinib treatment. Treatment of CML mice with imatinib (200mg/kg/day, 2 weeks) led to reduction in MIP1α, MIP1β, IL-1β, and IL-6 levels in BM cells. Engraftment of normal LTHSC was significantly enhanced in BM of CML recipients pre-treated with imatinib. Results obtained with the mouse model were validated using specimens obtained from CML patients. CXCL12 mRNA levels were significantly reduced in human CML compared to normal MNCs, whereas expression of MIP1α, MIP-2, IL-1α and IL-1β were increased in CML MNCs, consistent with results obtained with the mouse model. Coculture with CML MNC conditioned medium (CM) resulted in selective impairment of growth of normal CD34+CD38- primitive progenitors compared to CM from normal MNC, but did not inhibit growth of CML progenitors. We conclude that leukemia-induced alterations in BM cytokine and chemokine levels contribute to altered LSC lodgment and to selective impairment of growth of normal LTHSC in the CML BM microenvironment, leading to a relative growth advantage for CML LSC over normal LTHSC and expansion of the leukemic clone. Disclosures: Holyoake: Novartis: Research Funding; Bristol Myers Squibb: Research Funding.

scholarly journals Identification of small juvenile stem cells in aged bone marrow and their therapeutic potential for repair of the ischemic heart

2013 ◽  
Vol 305 (9) ◽  
pp. H1354-H1362 ◽  
Author(s):  
Koichi Igura ◽  
Motoi Okada ◽  
Ha Won Kim ◽  
Muhammad Ashraf
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Therapeutic Potential ◽  
Left Ventricular ◽  
Stem Cell Markers ◽  
Differentiation Potential ◽  
Small Juvenile ◽  
Cardiomyogenic Differentiation ◽  
Proliferation And Differentiation

Stem cell-mediated cardiac regeneration is impaired with age. In this study, we identified a novel subpopulation of small juvenile stem cells (SJSCs) isolated from aged bone marrow-derived stem cells (BMSCs) with high proliferation and differentiation potential. SJSCs expressed mesenchymal stem cell markers, CD29+/CD44+/CD59+/CD90+, but were negative for CD45−/CD117− as examined by flow cytometry analysis. SJSCs showed higher proliferation, colony formation, and differentiation abilities compared with BMSCs. We also observed that SJSCs significantly expressed cardiac lineage markers (Gata-4 and myocyte-specific enhancer factor 2C) and pluripotency markers (octamer-binding transcription factor 4, sex-determining region Y box 2, stage-specific embryonic antigen 1, and Nanog) as well as antiaging factors such as telomerase reverse transcriptase and sirtuin 1. Interestingly, SJSCs either from young or aged animals showed significantly longer telomere length as well as lower senescence-associated β-galactosidase expression, suggesting that SJSCs possess antiaging properties, whereas aged BMSCs have limited potential for proliferation and differentiation. Furthermore, transplantation of aged SJSCs into the infarcted rat heart significantly reduced the infarction size and improved left ventricular function, whereas transplantation of aged BMSCs was less effective. Moreover, neovascularization as well as cardiomyogenic differentiation in the peri-infarcted area were significantly increased in the SJSC-transplanted group compared with the BMSC-transplated group, as evaluated by immunohistochemical analysis. Taken together, these findings demonstrate that SJSCs possess characteristics of antiaging, pluripotency, and high proliferation and differentiation rates, and, therefore, these cells offer great therapeutic potential for repair of the injured myocardium.

scholarly journals Bone Marrow-Derived Stem Cells Protect against Haloperidol-Induced Brain and Liver Damage in Mice

2018 ◽  
Vol 11 (1) ◽  
pp. 11-22 ◽  
Author(s):  
Omar M. E. Abdel-Salam ◽  
Amany A. Sleem ◽  
Eman R. Youness ◽  
Nadia A. Mohammed ◽  
Enayat A. Omara
Keyword(s):  
Nitric Oxide ◽  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Liver Damage ◽  
Paraoxonase 1 ◽  
High Dose ◽  
Neuronal Necrosis ◽  
Tnf Α ◽  
Stem Cell Treatment

We studied the effect of bone marrow-derived stem cells (BM-SCs) on oxidative stress, inflammation and pathological changes induced in the brain and liver of mice by the antipsychotic drug haloperidol. Mice were intraperitoneally (i.p.) treated with haloperidol at 5 mg/kg for 3 consecutive days followed by i.p. stem cell suspension and euthanized 24h later. Haloperidol resulted in increased brain and liver malondialdehyde (MDA) and nitric oxide contents together with decreased reduced glutathione (GSH). There were also decreased paraoxonase-1 (PON-1) activity in brain and liver and increased interleukin-1β (IL-1 β), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in brain tissue. Haloperidol produced neuronal necrosis and apoptosis and the appearance of esinophilic areas and strong TNF-α immunoreactivity in the cerebral cortex and striatum of treated mice. In the liver, centrilobular necrosis, inflammatory cell infiltration and sinusoidal haemorrhage were observed. In haloperidol-treated mice, stem cell injection had no significant effects on brain and liver levels of MDA, nitric oxide or GSH. Paraoxonase-1 activity in brain, however, decreased by stem cells application. In brain, there were decreased IL-1β, IL-6 and TNF-α. Brain neurodegenerative changes, brain TNF-immunoreactivity and histological liver damage were all markedly ameliorated after stem cell treatment. These results indicate that stem cells protect against brain and liver toxicity caused by short term haloperidol treatment in high dose. The protective effects of stem cell treatment is likely to result from interfering with cytokine release.

59 Deficiency of Bone Marrow Derived TNF α Impairs Stem Cell Activation and Promotes Apoptosis in Murine Small Intestine Following T Cell Activation

2009 ◽  
Vol 136 (5) ◽  
pp. A-10
Author(s):  
Ajaypal Singh ◽  
Mutazz Darweesh ◽  
Goo Lee ◽  
Ramanarao Dirisina ◽  
Rebecca B. Katzman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Small Intestine ◽  
Stem Cell ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Tnf Α ◽  
Murine Small Intestine

TNF-α Increases Bone Marrow Mesenchymal Stem Cell Migration to Ischemic Tissues

2011 ◽  
Vol 62 (3) ◽  
pp. 409-414 ◽  
Author(s):  
Qiong Xiao ◽  
Shi-kun Wang ◽  
Hua Tian ◽  
Li Xin ◽  
Zhi-geng Zou ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Cell Migration ◽  
Mesenchymal Stem Cell ◽  
Stem Cell Migration ◽  
Tnf Α

scholarly journals Bone Marrow Stem Cell Derived Paracrine Factors for Regenerative Medicine: Current Perspectives and Therapeutic Potential

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Tom J. Burdon ◽  
Arghya Paul ◽  
Nicolas Noiseux ◽  
Satya Prakash ◽  
Dominique Shum-Tim
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Cell Therapy ◽  
Therapeutic Potential ◽  
Paracrine Factors ◽  
Beneficial Effects ◽  
Cytokines And Chemokines ◽  
Survival Pathways ◽  
Wide Range ◽  
Technical Issues

During the past several years, there has been intense research in the field of bone marrow-derived stem cell (BMSC) therapy to facilitate its translation into clinical setting. Although a lot has been accomplished, plenty of challenges lie ahead. Furthermore, there is a growing body of evidence showing that administration of BMSC-derived conditioned media (BMSC-CM) can recapitulate the beneficial effects observed after stem cell therapy. BMSCs produce a wide range of cytokines and chemokines that have, until now, shown extensive therapeutic potential. These paracrine mechanisms could be as diverse as stimulating receptor-mediated survival pathways, inducing stem cell homing and differentiation or regulating the anti-inflammatory effects in wounded areas. The current review reflects the rapid shift of interest from BMSC to BMSC-CM to alleviate many logistical and technical issues regarding cell therapy and evaluates its future potential as an effective regenerative therapy.

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