scholarly journals Downregulation of extracellular vesicle microRNA‑101 derived from bone marrow mesenchymal stromal cells in myelodysplastic syndrome with disease progression

2020 ◽  
Author(s):  
Yuu Saitoh ◽  
Tomohiro Umezu ◽  
Satoshi Imanishi ◽  
Michiyo Asano ◽  
Seiichiro Yoshizawa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Disease Progression ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Extracellular Vesicle

Mesenchymal Stromal Cells From Myelodysplastic Syndrome Patients Show Lower DICER1 and DROSHA Expression, as Well as Decreased Mir-155 and Mir-181a MicroRNA Expression, When Compared with Healthy Controls

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 397-397
Author(s):  
Carlos Santamaría ◽  
Olga López-VIllar ◽  
Sandra Muntión ◽  
Belén Blanco ◽  
Soraya Carrancio ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Protein Expression ◽  
Myelodysplastic Syndrome ◽  
Western Blot ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Microrna Expression ◽  
Healthy Controls ◽  
Lower Expression

Abstract Abstract 397 Mesenchymal stromal cells (MSC) are closely related to the regulation of hematopoietic stem cell niche. Recently, Raaijmakers et al (Nature, 2010), published that deletion of Dicer1, a RNase III enzyme involved in microRNA biogenesis, in murine MSC-derived osteoprogenitors triggered peripherical blood cytopenias, myelodysplasia and subsequent AML, showing that molecular alterations in bone marrow microenvironment could result in clonal impaired haematopoiesis. Here, we have investigated whether MSC from myelodysplastic syndrome (MDS) patients show differences in DICER1 and DROSHA, another RNA III endonuclease, in comparison to healthy MSC. In addition, we have analyzed several hematopoietic-related microRNAs in these same samples. Bone marrow MSC from MDS patients (n=35; 10 5q- syndrome, 4 RA, 5 RARS, 10 RCMD, 3 RAEB, 2 MDS-U and 1 hypocellular MDS) and healthy donors (HD, n=20) were isolated and in vitro expanded following standard procedures until the third passage. Additionally, paired mononuclear cells (MNC) from 13 MDS and 8 HD were obtained. Total RNA was isolated using TRIzol reagent (Invitrogen). DICER1 and DROSHA relative gene expressions were assessed by quantitative PCR (Q-PCR) using commercial TaqMan® assay (Applied Biosystems®) with GAPDH as control gene. DICER1 and DROSHA (Abcam) protein expression were evaluated in whole cell lysates by western blot, using calnexin (Stressgen) as control. Several microRNAs with known role in hematopoiesis and immune system regulation were analyzed in 25 MDS and 12 HD by Q-PCR using commercial TaqMan® MicroRNA assay (Applied Biosystems®) with RNU43 as control microRNA. MSC from MDS showed significant lower DICER1 (0.0035±0.0020 vs. 0.0076±0.0092; p=0.044) and DROSHA (0.0070±0.0028 vs. 0.0135±0.0176; p=0.019) gene expression levels than healthy controls. Moreover, MSC from MDS showed lower protein expression of both DICER1 and DROSHA by western blot analysis, confirming Q-PCR findings. By contrast, no difference in either DICER1 (0.0197±0.0151 vs. 0.0173±0.0112; p=0.9) or DROSHA (0.0089±0.0023 vs. 0.0067±0.0037; p=0.09) gene expression were observed between MNC from MDS and HD. As far as microRNA expression, we observed a lower expression of mir-155 (0.63±0.92 vs. 0.94±0.49; p=0.007) and mir-181a (1.30±0.95 vs. 2.02±1.05; p=0.041) in MSC from MDS in comparison to healthy controls. Mir-155 and mir-181a are involved in T-cell and B-cell differentiation, while mir-155 are also related to erythroid and megakarycytic differentiation. We conclude that MSC from MDS patients show lower expression of DICER and DROSHA, two relevant RNA-III endonucleases involved in the microRNA biogenesis, confirming recent findings in murine models. Moreover, the expression of some microRNA is impaired in these cells, raising the possibility that these microenvironmental alterations could be involved in the MDS pathophysiology. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Common and different alterations of bone marrow mesenchymal stromal cells in myelodysplastic syndrome and multiple myeloma

2020 ◽  
Vol 53 (5) ◽  
Author(s):  
Hayoung Choi ◽  
Yonggoo Kim ◽  
Dain Kang ◽  
Ahlm Kwon ◽  
Jiyeon Kim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells

scholarly journals Sonic Hedgehog Produced by Bone Marrow-Derived Mesenchymal Stromal Cells Supports Cell Survival in Myelodysplastic Syndrome

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Jixue Zou ◽  
Yan Hong ◽  
Yin Tong ◽  
Ju Wei ◽  
Youwen Qin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Cell Survival ◽  
Sonic Hedgehog ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Shh Signaling ◽  
High Risk Factors

The role of marrow microenvironment in the pathogenesis of myelodysplastic syndrome (MDS) remains controversial. Therefore, we studied the influence of bone marrow-derived mesenchymal stromal cells (BMSCs) from patients with different risk types of MDS on the survival of the MDS cell lines SKM-1 and MUTZ-1. We first demonstrated that the expression of Sonic hedgehog (Shh), smoothened (Smo), and glioma-associated oncogene homolog 1 (Gli1) was increased in MDS patientsn=23; the increase in expression was positively correlated with the presence of high-risk factors. The Shh signaling inhibitor, cyclopamine, inhibited high-risk MDS BMSC-induced survival of SKM-1 and MUTZ-1 cells, suggesting a role for Shh signaling in MDS cell survival. Furthermore, cyclopamine-mediated inhibition of Shh signaling in SKM-1 and MUTZ-1 cells resulted in decreased DNMT1 expression and cell survival; however, exogenous Shh peptide had the opposite effect, suggesting that Shh signaling could regulate the expression of DNMT1, thereby modulating cell survival in MDS. In addition, the apoptosis of SKM-1 and MUTZ-1 cell increased significantly when cultured with cyclopamine and a demethylation agent, 5-Aza-2′-deoxycytidine. These findings suggest that Shh signaling from BMSCs is important in the pathogenesis of MDS and could play a role in disease progression by modulating methylation.

scholarly journals Renal Regenerative Potential of Different Extracellular Vesicle Populations Derived from Bone Marrow Mesenchymal Stromal Cells

2017 ◽  
Vol 23 (21-22) ◽  
pp. 1262-1273 ◽  
Author(s):  
Stefania Bruno ◽  
Marta Tapparo ◽  
Federica Collino ◽  
Giulia Chiabotto ◽  
Maria Chiara Deregibus ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Extracellular Vesicle

Mechanisms of action and osteogenic activity of bone marrow mesenchymal stromal cells are donor dependent

2014 ◽  
Author(s):  
Julie Leotot ◽  
Angelique Lebouvier ◽  
Philippe Hernigou ◽  
Helene Rouard ◽  
Nathalie Chevallier
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Mechanisms Of Action ◽  
Osteogenic Activity
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