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Human Mesenchymal Stem / Stromal Cells (hMSCs) treated with Eltrombopag show increase of the hematopoietic supporting ability

ABSTRACT: Human Mesenchymal Stem / Stromal Cells (hMSCs) treated with Eltrombopag show increase of the hematopoietic supporting ability

PROVIDER: PRJNA834765 | ENA |

REPOSITORIES: ENA

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Human Mesenchymal Stem / Stromal Cells (hMSCs) treated with Eltrombopag show increase of the hematopoietic supporting ability

Project description:Eltrombopag (EP) is a small molecule that acts on hematopoietic cells and megakaryocytes to stimulate the hematopoiesis. Mesenchymal stem/stromal cells (MSCs) are key hematopoietic niche regulators. In the current work we aimed to assess if EP exert any effect on MSCs function, especially on their hematopoietic-supporting ability, and if so, what are the changes (including transcriptomic) induced in MSCs after EP treatment. For this purpose, MSCs were isolated from 12 healthy donors and treated with 15 uM and 50 uM of EP for 24 hours. The toxicity of the drug on MSCs and their differentiation ability were analyzed, as well as the transcriptomic profile, ROS and DNA damage and finally the changes induced in the clonogenic capacity of HSC. We observed that EP acts on MSCs decreasing their adipogenic differentiation, increasing the expression of genes involved in hypoxia and other pathways and enhancing their ability to support hematopoiesis. We used high density oligo microarrays (Affymetrix Clariom_S_Human) to obtain the global programme of gene expression underlying the effect of the Eltrombopag (EP) and Thrombopoietin (TPO) in human MSCs (derived from bone marrow) and identify the genes activity.

2023-01-07 | GSE202127 | GEO

Identification of differentially expressed genes upon treatment with Eltrombopag in HL60 cells

Project description:Identification of differentially expressed genes upon treatment with Eltrombopag in HL60 cells. HL60 cells were untreated, or treated with 3ug/ml of Eltrombopag for 36 hrs in RPMI with 10% FBS HL60 cells were untreated, or treated with 3ug/ml of Eltrombopag for 36 hrs in RPMI with 10% FBS

2012-06-24 | E-GEOD-37580 | biostudies-arrayexpress

Gene expression profiling of mouse HSCs treated with Eltrombopag

Project description:Eltrombopag, a small molecule thrombopoietin receptor (TPO-R) agonist and potent intracellular iron chelator, has shown remarkable efficacy to stimulate sustained multilineage hematopoiesis in patients with bone marrow failure syndromes, suggesting an effect at the most immature hematopoietic stem and multipotent progenitor level. While the functional and molecular effects of Eltrombopag on megakaryopoiesis have been carefully studied in the recent past, insights into its mechanistic impact on the earliest stages of hematopoiesis have been limited. Additionally, previous studies also revealed molecular pathway of Eltrombopag apart from stimulation of TPO signaling, detail characterization remains to be addressed. In this study, we investigated the effects of Eltrombopag, in comparison with TPO, on highly-purified primary hematopoietic stem cells (HSCs) from healthy human donors. The binding of Eltrombopag to TPO-R is species-specific to human and primate cells. we also utilized HSCs isolated mouse as separation-of-function models to directly assess the molecular effect of Eltrombopag on HSCs independent of TPOR stimulation.

2018-09-17 | GSE107429 | GEO

Gene expression profiling of human HSCs treated with Eltrombopag

2018-09-17 | GSE107428 | GEO

Identification of differentially expressed genes upon treatment with Eltrombopag in HL60 cells

2012-06-25 | GSE37580 | GEO

RNA sequencing of Cryptococcus neoformans H99 treated with eltrombopag

Project description:The gene expression of C. neoformans H99 treated with eltrombopag

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Human Mesenchymal Stem Cells (hMSCs): Fibroblast vs. hMSCs from various origins

Project description:To identify the key microRNAs (miRNAs) of hMSCs required for fate determination, miRNA profiling was performed with hMSCs from three different sources including adipose-derived stem cells (ADSCs), bone-marrow-derived stem cells (BMSCs), and umbilical cord-derived stem cells (UCSCs) versus fibroblasts, a more differentiated mesenchymal cell types. We compared the expression profiles of two different donors per hMSCs to that of fibroblasts. All hMSCs were used for profiling at passage 3-6.

2014-05-05 | E-GEOD-57266 | biostudies-arrayexpress

Blood transcriptome and clonal T cell correlates of response and nonresponse to eltrombopag therapy in a cohort of patients with chronic immune thrombocytopenia

Project description:We evaluated the longitudinal effect of eltrombopag, a thrombopoietin receptor agonist, on gene expression in heavily pretreated patients with chronic immune thrombocytopenia (ITP) using blood transcriptome analysis on pretreatment, and following 1 week and 1 month of treatment samples. A strong stimulation of 208 eltrombopag-induced genes was identified in responders at 1-week time point. 90% of these genes are present in platelets, with GATA1, THPO, VIPAS39 and TGFB1 as top upstream regulators. Subsequently, despite a continued increase in platelet in responders, the eltrombopag-induced gene expression decreased at 1 month compared with the level at 1-week time point. This novel observation of the longitudinal effect of eltrombopag therapy over time suggests different stages of eltrombopag response. Non-responders did not exhibit eltrombopag-induced gene expression changes. This study provides novel insights into the mechanisms of eltrombopag response and nonresponse.

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Lateral mesoderm-derived mesenchymal stem cells with robust osteochondrogenic potential and hematopoiesis supporting ability

Project description:Lateral mesoderm-derived mesenchymal stem cells with robust osteochondrogenic potential and hematopoiesis supporting ability

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Human Mesenchymal Stem Cells (hMSCs): Fibroblast vs. hMSCs from various origins

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