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Gene expression profiling of mesenchymal stem cells from bone marrow of multiple myeloma patients and normal donors

ABSTRACT: A growing body of evidence points to the essential role of bone marrow (BM) tumor microenvironment in Multiple Myeloma (MM) maintenance and progression. Mesenchymal stem cells (MSC) are one of the most important players in this scenario. Through direct and indirect interactions, these cells support MM cells by promoting increase of proliferation, migration, survival, and drug resistance. Additionally, an increasing number of evidence has been demonstrating that MSC from MM patients (MM-MSC) have several abnormalities when compared with their normal counterpart from normal donors (ND-MSC). Therefore, the aimed of our study was to explore the differences between MM-MSC and ND-MSC through gene expression analysis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE113736 | GEO | 2019/01/21

REPOSITORIES: GEO

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Expression data from bone marrow mesenchymal stromal cells obtained from healthy donors and myeloma patients

Project description:Multiple myeloma (MM) is a B-cell neoplasm characterized by clonal expansion of malignant plasma cells (MM cells) in the bone marrow (BM) compartment, where they acquire resistance to chemotherapy-mediated apoptosis. Natural history of patients include a premalignant stage, the MM diagnosis, the treatment, the remission, and for most of them the relapse. BM mesenchymal stromal cells (MSC) from newly diagnosed MM patients are functionally different from healthy donors (HD) MSC and display a distinct transcriptome. They have been largely involved in MM pathogenesis and chemoresistance acquisition. In order to determine if MM-MSC also participate to relapse, we focused on the characterization of MSC from patients with MM at different stages of the disease. We obtained patient MSC’s samples at diagnosis, at 2 years after intensive treatment without relapse and at the relapse from an intensive treatment. We used MCS from HD as control. All MSC were able to support MM cells growth through released factors, and still multipotent since able to differentiate into osteoblast and adipocyte. A transcriptomic analysis between these groups reveals differences in gene expression between HD and MM MSC whatever stage of the disease, suggesting that the difference in gene expression in MM-MSC persist with time. These data demonstrate an imprinting of MSC as soon as they were in contact with MM cells, which persist even after the disappearance of MM cells. This imprinting is in favour of an easier differentiation towards adipogenesis.

2021-12-30 | GSE146649 | GEO

Functional comparison between healthy and multiple myeloma adipose stromal cells

Project description:Multiple myeloma (MM) is a not curable B-cell neoplasia characterised by the accumulation of tumor plasma cells within the bone marrow. As a consequence, 80% of patients develop bone osteolytic lesions that remain even after complete remission. We and others had demonstrated that bone marrow derived Mesenchymal Stromal Cells (MSC) are abnormal in MM and thus could not be used for an autologous treatment to repare bone damages. Adipose Stromal Cells (ASC) represent an interesting alternative to MSC for cellular therapy. Thus, in this paper we asked if they could be a good candidate in repairing MM bone lesions. For the first time, we present a transcriptomic, phenotypic and functional comparison between ASC from MM patients and healthy donors (HD) relying on their autologous MSC counterpart. In contrast to MM MSC, MM ASC do not exhibit major abnormalities. However, the changes observed in MM ASC and the supportive property of ASC on MM cells question their putative and safety uses at autologous or allogenic level.

2019-06-27 | GSE133346 | GEO

The proteome data of human mesenchymal stem cell derived from healthy donors

Project description:The protein samples stored at -80 °C were thawed and treated with lysis buffer (8M urea, 1% protease inhibitor, 50mM NH4HCO3) for 5 minutes in room temperature. After ultrasonic cracking on ice and centrifugation at 14000g for 10 min at 20 °C, the amount of total protein of each MSC sample was detected by bicinchoninic acid assay (Beijing Solarbio Science & Technology Co., Ltd., Beijing, China) using NanoDrop ND-1000 spectrophotometer (Thermo Fisher Scientific, Inc., Sunnyvale, CA, USA). Protein digestion was carried out by a filter-aided sample preparation technique. Briefly, 50 μg of a sample was loaded onto a Microcon filter unit YM-30 (Millipore) and washed with 8 M urea, followed by protein alkylation with 50 mM iodoacetamide in 8 M urea in darkness for 20 min. After alkylation, the filters were washed twice with 8 M urea and twice with 40 mM ammonium bicarbonate. Trypsin (Promega, Madison, WI, USA) was added to the samples at 100:1 protein-to-enzyme ratio and incubated overnight at 37 °C. Later the same

2023-06-12 | PXD033812 | iProX

MicroRNA expression changes in Bone Marrow Stromal Cells from Myeloma Patients vs Normal Patients, and From Normal Patients cultured with or without Myeloma cells in 3D culture

Project description:The objectives of this study were to assess differences in Bone Marrow Derived Menenchymal Stromal Cells (MSCs) during co-culture with myeloma cells, and to assess differences in myeloma patient MSCs compared to normal donor MSCs. In the study presented here, a Bone Marrow Derived Menenchymal Stromal Cells (MSCs) were analyzed after FACS sorting from 2 week culture in osteogenic media lacking dexamethasone in 3D silk scaffold matrices either in co-culture with the multiple myeloma cell line GFP+Luc+MM1.S or Alone, as controls. Also, monocultures of MSCs grown in 2D, in MSC expansion media, from Normal Donor Controls (ND) or Multiple myeloma patients (MM) were analyzed. Analysis was done looking at microRNA expression in samples with the nanoString microRNA platform for 800 microRNAs.

2014-11-01 | E-GEOD-60423 | biostudies-arrayexpress

Molecular profiling of Ebf2+ and Ebf2- PαS mesenchymal stem cells from mouse dorsal skin

Project description:While extensive efforts have been on understanding bone marrow (BM) niche contribution to normal and malignant hematopoiesis, the role of extramedullary niches has been largely ignored. Evidence suggests a BM mesenchymal stem cell (MSC) counterpart exists in skin. However, their native identity and role in hematopoiesis remain unexplored. Here, we demonstrated that mouse skin harbors MSC subsets that are phenotypically and molecularly similar to BM MSCs, including a primitive MSC population marked by Early B-cell Factor 2 (Ebf2) and downstream MSCs lacking Ebf2. Functionally, skin MSCs not only support acute myeloid leukemia (AML) stem cells but also protect them from chemotherapy. This persistence of AML cells in skin were further amplified in AML-promoting microenvironment lacking Lama4. Our study demonstrated the features of extramedullary niches in skin and their previously unrecognized role in supporting AML stem cells during chemotherapy, opening a new path for understanding the extramedullary manifestation of AML in patients.

2023-07-16 | GSE167562 | GEO

bulk RNA-seq data analysis of primary human mesenchymal stem cells of Multiple Myeloma patients compared to control patients

Project description:Purpose: In this study we compared bone marrow-derived mesenchymal stem cells (MSC) of 6 Multiple Myeloma patients (MM-MSC) with MSC of 5 control donors with other (non) malignant diseases (CTR-MSC) to detect transciptomic alterations in RNA sequencing and to identify altered gene expression patterns. Methods: MSC were obtained from bone marrow, cultivated, analyzed by flow cytometry and underwent quality control using the 4200 TapeStation (Agilent, California, USA). Following the TrueSeq stranded protocol (Illumina, California, USA) we sequenced the RNA in a 100 bp paired-end run on the HiSeq 4000 (Illumina). Results: We detected 2174 significant DEGs (adjusted p<0.05) between MM-MSC and CTR-MSC, among which 967 were up-regulated in MM-MSC. 18 out of 50 MSigDB Hallmark gene sets were significantly enriched in MM-Act-MSC compared to CTR-MSC (FDR<0.05) including PI3K-AKT-mTOR signaling, as well as NOTCH, MYC and Inflammatory response. Conclusion: Our data provides a deeper insight into the molecular signature and function of MSC associated MM-cells and show that targeting PI3K-AKT-mTOR signaling in MSC may represent an additional therapeutic pathway in the treatment of MM-patients.

2022-05-13 | GSE196297 | GEO

Expression data from exosomes

2013-07-24 | GSE39571 | GEO

Comparison of bone-marrow mesenchymal stromal cells from multiple myeloma patients and healthy donors

Project description:It is now well established that bone marrow (BM) constitutes a microenvironment required for differentiation. Bone marrow mesenchymal stromal cells (BM-MSCs) strongly support MM cell growth, by producing a high level of Interleukin-6 (IL-6), a major MM cell growth factor. BM-MSCs also support osteoclastogenesis and angiogenesis. Previous studies have suggested that the direct (VLA-4, VCAM-1, CD44, VLA-5, LFA-1, syndecan-1,…) and indirect interactions (soluble factors) between MM plasma cells and BM-MSCs result in constitutive abnormalities in BM-MSCs. In particular, MM BM-MSCs express less CD106 and fibronectin and more DKK1, IL-1β and TNF-α as compared with normal BM-MSCs. In order to gain a global view of the differences between BM-MSCs from MM patients and healthy donors, we used gene expression profiling to identify genes associated to the transformation of MM BM-MSCs.

2013-03-21 | GSE36474 | GEO

Expression data from exosomes

Project description:Bone marrow (BM) niches provide an optimal substrate for multiple myeloma (MM) cell lodgement and growth. Nevertheless, little is known about the putative mechanisms by which the BM microenvironment can lead to initiation or progression of oncogenesis in this disease. We have demonstrated that BM mesenchymal stromal cell-derived exosomes transfer their miRNA and protein content to clonal plasma cells, thus acting as synaptic vesicles responsible for molding the microenvironment surrounding multiple myeloma (MM) cells, leading to MM growth, dissemination and, therefore, disease progression. We used microarray to detail the changes in microRNA expression in MM-BM mesenchymal stromal cell (MSC)-derived exosomes, compared to normal- and monoclonal gammopathy of undetermined significance- BM-MSC-derived exosomes. Exosomes have been isolated from cell culture supernatant of BM-MSCs (MM=7; MGUS=2; Normal=4), and subsequently evaluated at ultrastructural level by using electron microscopy and immunogolf labeling. RNA was extracted; and miRNA profiling has been assessed by using TaqMan human miRNA profiling. Mean miRNA expression value has been used for miRNA RT-qPCR data normalization, as described (Mestdagh et al., 2009).

2013-07-24 | E-GEOD-39571 | biostudies-arrayexpress

Genome wide expression profiling of mesenchymal stem cells of fetal and adult origin and dermal fibroblasts

Project description:In animal models and human trials, intramyocardial injection of adult bone-marrow derived mesenchymal stem cells (BM-MSC) provides beneficial effects in failing hearts. These effects are mainly mediated through paracrine mechanisms. Mesenchymal stem cells of fetal origin (hAMC) can be isolated from the amniotic membrane of human placenta. Our results provide evidence that hAMC exert remarkable cardioprotective effects through paracrine mechanisms. However, the complete nature and scope of the paracrine mediators of cardioprotection have not been investigated yet. We compared the gene expression profiling of hAMC (n=8), BM-MSC (n=10) and dermal fibroblasts (n=6) to shed light onto the identity of putative cardioprotective factors secreted by fetal MSC. Total RNA was extracted from cultured hAMC (n=8), BM-MSC (n=10) and dermal fibroblasts (n=6) and analyzed with HumanHT-12 v3 Expression BeadChips

2015-06-15 | E-GEOD-61153 | biostudies-arrayexpress

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