Effect of 17β-estradiol on mediators involved in mesenchymal stromal cell trafficking in cell therapy of diabetes

Mirzamohammadi, Solmaz; Aali, Ehsan; Najafi, Rezvan; Kamarul, Tunku; Mehrabani, Mehrnaz; Aminzadeh, Azadeh; Sharifi, Ali Mohammad

doi:10.1016/j.jcyt.2014.06.009

Cited by 24 publications

(15 citation statements)

References 57 publications

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“…In low O2 tension, HIF‐1α is stabilized and translocated to the nucleus and binds to HIF‐1β. This complex is associated with HRE in DNA and regulates the transcription of genes involved in stem cell survival, metabolism, invasion and angiogenesis, including VEGF, SDF‐1 and erythropoietin …”

Section: Discussionmentioning

confidence: 99%

Cytoprotective effects of endothelin‐1 on mesenchymal stem cells: an in vitro study

Pourjafar

Saidijam

Mansouri

et al. 2016

Clin Exp Pharma Physio

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Stem cell-based therapies is a promising approach for regenerative therapy in various diseases. Some obstacles remain to be solved before clinical application of the cell therapy is realized, including increasing the survival of transplanted stem cells, reducing loss of transplanted cells, and maintaining adequate vascular supply. Recently, stem cell preconditioning with chemical and pharmacological agents has been shown to increase therapeutic efficacy. The present study investigated the effect of endothelin-1 (ET-1) on survival, angiogenesis, and migration of mesenchymal stem cells (MSCs), in vitro. MSCs were treated with various concentrations of ET-1 and the expression of cyclooxygenase-2 (COX-2), hypoxia-inducible factor-1 (HIF-1), C-X-C chemokine receptor type 4 (CXCR4), C-C chemokine receptor type 2 (CCR2), vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), angiopoietin-4 (Ang-4) and matrix metalloproteinase-2 (MMP-2) were examined. Caspase 3 activity and prostaglandin E2 (PGE2) were determined by ELISA assay. MSCs migration and tube formation potential were assessed using scratch test and three dimensional vessel formation assay. ET-1 enhanced the MSCs viability. In ET-1- treated MSCs, expression of COX-2, HIF-1, CXCR4, CCR2, VEGF, Ang-2, Ang-4 and MMP-2 were increased compared to control groups. Elevation of all these genes were reversed by celecoxib (50 μmol/L), a selective COX-2 inhibitor. PGE2 generation, MSCs migration and tube formation were enhanced by ET-1 conditioning, whereas caspase-3 activity was reduced in these cells, compared to the control group. The results presented here reveal that preconditioning of MSCs with ET-1 has strong cytoprotective effects through activation of survival signalling molecules and trophic factors.

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Section: Discussionmentioning

confidence: 99%

Cytoprotective effects of endothelin‐1 on mesenchymal stem cells: an in vitro study

Pourjafar

Saidijam

Mansouri

et al. 2016

Clin Exp Pharma Physio

Self Cite

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“…Western blot analysis was conducted as described previously [Mirzamohammadi et al, 2015]. Briefly, following stimulation, nontreated and treated cells were tripsinized and rinsed centrifugally twice with ice-cold PBS.…”

Section: Protein Extraction/western Blot Analysismentioning

confidence: 99%

Protective Effect of Ginger (<b><i>Zingiber officinale</i></b> Roscoe) Extract against Oxidative Stress and Mitochondrial Apoptosis Induced by Interleukin-1β in Cultured Chondrocytes

Hosseinzadeh

Juybari

Fatemi

et al. 2017

Cells Tissues Organs

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Aims: The protective effects of ginger (Zingiber officinale Roscoe) extract on IL-1β-mediated oxidative stress and mitochondrial apoptosis were investigated in C28I2 human chondrocytes. Methods: The effects of various concentrations of ginger extract on C28I2 human chondrocyte viability were evaluated in order to obtain noncytotoxic concentrations of the drug by methylthiotetrazole assay. The cells were pretreated with 5 and 25 μg/mL ginger extract for 24 h, followed by incubation with IL-1β (10 ng/mL) for 24 h. The effects of ginger extract on IL-1β-induced intracellular reactive oxygen species (ROS) production and lipid peroxidation were examined. The mRNA expressions of antioxidant enzymes including catalase, superoxide dismutase-1, glutathione peroxidase-1, glutathione peroxidase-3, and glutathione peroxidase-4 were evaluated by reverse transcription polymerase chain reaction. The protein expressions of Bax, Bcl-2, and caspase-3 were analyzed by Western blotting. Results: No cytotoxicity was observed at any concentration of ginger extract in C28I2 cells. Ginger extract pretreatment remarkably increased the gene expression of antioxidant enzymes and reduced the IL-1β-induced elevation of ROS, lipid peroxidation, the Bax/Bcl-2 ratio, and caspase-3 activity. Conclusions: Ginger extract could considerably reduce IL-1β-induced oxidative stress and consequent mitochondrial apoptosis as the major mechanisms of chondrocyte cell death. These beneficial effects of ginger extract may be due to its antioxidant properties. It may be considered as a natural herbal product to prevent OA-induced cartilage destruction in the clinical setting.

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“…For instance, incubating MSCs in conditioned supernatant from irradiated cancer cells can enhance tumor targeting by upregulating the expression of multiple chemokine receptors, including CCR2 70 . HIF1-dependent upregulation of CXCL12 and CXCR4 in MSCs using preconditioning regimens including hypoxia, cobalt chloride and estrogen increase MSC trafficking to injured tissue 71–74 . Furthermore, we intend to explore multiple cell bioengineering approaches previously established in our laboratory such as surface chemical modification, mRNA transfection and small molecule pretreatment 75,76 to express homing ligands on the cell surface and maximize targeting of systemically infused cells to sites of PCa metastasis.…”

Section: Resultsmentioning

confidence: 99%

A prodrug-doped cellular Trojan Horse for the potential treatment of prostate cancer

et al. 2016

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Despite considerable advances in prostate cancer research, there is a major need for a systemic delivery platform that efficiently targets anti-cancer drugs to sites of disseminated prostate cancer while minimizing host toxicity. In this proof-of-principle study, human mesenchymal stem cells (MSCs) were loaded with poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) that encapsulate the macromolecule G114, a thapsigargin-based prostate specific antigen (PSA)-activated prodrug . G114-particles (~950nm in size) were internalized by MSCs, followed by the release of G114 as an intact prodrug from loaded cells. Moreover, G114 released from G114 MP-loaded MSCs selectively induced death of the PSA-secreting PCa cell line, LNCaP. Finally, G114 MP-loaded MSCs inhibited tumor growth when used in proof-of-concept co-inoculation studies with CWR22 PCa xenografts, suggesting that cell-based delivery of G114 did not compromise the potency of this pro-drug in-vitro or in-vivo. This study demonstrates a potentially promising approach to assemble a cell-based drug delivery platform, which inhibits cancer growth in-vivo without the need of genetic engineering. We envision that upon achieving efficient homing of systemically infused MSCs to cancer sites, this MSC-based platform may be developed into an effective, systemic ‘Trojan Horse’ therapy for targeted delivery of therapeutic agents to sites of metastatic PCa.

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Effect of 17β-estradiol on mediators involved in mesenchymal stromal cell trafficking in cell therapy of diabetes

Cited by 24 publications

References 57 publications

Cytoprotective effects of endothelin‐1 on mesenchymal stem cells: an in vitro study

Cytoprotective effects of endothelin‐1 on mesenchymal stem cells: an in vitro study

Protective Effect of Ginger (<b><i>Zingiber officinale</i></b> Roscoe) Extract against Oxidative Stress and Mitochondrial Apoptosis Induced by Interleukin-1β in Cultured Chondrocytes

A prodrug-doped cellular Trojan Horse for the potential treatment of prostate cancer

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