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Loss of immunosuppressive and anti-inflammatory properties in transformed human mesenchymal stem cells

ABSTRACT: We used collection of sequentially mutated BM-hMSCs ranging from wild type (no oncogenic hits) to fully transformed hMSCs (targeted with up six oncogenic mutations)to address whether BM-hMSCs at different stages of a well-characterized oncogenic process (normal, immortalized, transformed) retain immunomodulatory properties in vitro and in vivo. We characterize, for the first time, an oncogenic transformation-associated loss of the immunesuppressive and anti-inflammatory properties by hMSCs and identify candidate immune effectors underlying the loss of immunomodulation in transformed hMSCs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE55108 | GEO | 2015/05/14

SECONDARY ACCESSION(S): PRJNA238542

REPOSITORIES: GEO

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Expression of FUS-CHOP fusion protein in immortalized/transformed human Mesenchymal Stem Cells drives mixoid liposarcoma formation

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Expression of FUS-CHOP fusion protein in immortalized/transformed human Mesenchymal Stem Cells drives mixoid liposarcoma formation

Project description:Although different sarcomas have been modeled in mice upon expression of fusion oncogenes in MSCs, sarcomagenesis has not been successfully modeled in human MSCs (hMSCs). We report that FUS-CHOP, a hallmark fusion gene in mixoid liposarcoma (MLS), has an instructive role in lineage commitment, and its expression in hMSC sequentially immortalized/transformed with up to 5 oncogenic hits (p53 and Rb deficiency, hTERT over-expression, c-myc stabilization and H-RASv12 mutation) drives the formation of serially transplantable MLS. This is the first model of sarcoma based on the expression of a sarcoma-associated fusion protein in hMSC, and allowed us to unravel the differentiation processes and signaling pathways altered in the MLS-initiating cells. This study will contribute to test novel therapeutic approaches, and constitutes a proof-of-concept to employ hMSCs as target cell for modeling other fusion gene-associated human sarcomas. Wild type (MSC-0H) or transformed (MSC-5H) BM-hMSCs were transduced with concentrated viral particles expressing either pRRL-EF1?-PGK-GFP (empty vector; GFP) or pRRL-EF1?-FUS-CHOP-PGK-GFP (FUSCHOP expressing vector; FC) in order to generate MSC-0H-GFP, MSC-0H-FC, MSC-5H-GFP and MSC-5H-FC cell lines. MSC-0H-GFP and MSC-0H-FC cells did not develop tumors, meanwhile MSC-5H-GFP cells gave rise to undifferentiated sarcomas and MSC-5H-FC originated mixoid liposarcoma tumors when inoculated into immunedeficient mice. Several cell lines were derived from tumors developed from MSC-5H-GFP (T-5H-GFP-1 to -3 cell lines) and MSC-5H-FC (T-5H-FC-1 to -3 cell lines) cells. Gene expression analysis was performed using MSC-0H, MSC-5H and T-5H cell lines and lists of differentially expressed genes were created by comparing the gene expression profiles of MSC-0H-FC, MSC-5H-FC and T-5H-FC cell types to the control MSC-0H-GFP cells.

2013-06-18 | E-GEOD-48030 | biostudies-arrayexpress

Genome-wide pairwise analysis of normal and spontaneously transformed adipose tissue derived human multipotent stromal cells (hMSC)

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Differentially expressed genes between oncogene-transformed and non-transformed fetal liver progenitor cells

2013-02-02 | GSE43991 | GEO

Differentially expressed genes between oncogene-transformed and non-transformed fetal liver progenitor cells

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2013-02-02 | E-GEOD-43991 | biostudies-arrayexpress

Transformed cells after senescence give rise to more severe tumor phenotypes than transformed non-senescent cells

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2008-07-11 | GSE11756 | GEO

Genome-wide pairwise analysis of normal and spontaneously transformed adipose tissue derived hMSCs

Project description:hMSCs are perspective source for applications in the field of regeneraitve medicine. Biosafety of cultivated in vitro multipotent cells prior transplantation is one of the important issues. Genome-wide pairwise expression analysis of normal and immortalized hMSCs was performed to determine aspects of spontaneous transformation and immortalization mechanisms during cultivation of hMSCs. Data has provided insight into functionally connected genes involved in spontaneous transformation of hMSCs in vitro. Multipotent stromal cells (MSCs) were isolated from adipose tissue samples obtained from 6 healthy donors. Total RNA was isolated from 6 normal and 6 donor-matched spontaneously transformed hMSC cultures in vitro for pair-wise global comparison.

2012-12-09 | E-GEOD-42809 | biostudies-arrayexpress

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Quantitative Proteomics Reveals Metabolic Differences in Homing and Non-Homing Glioma Stem Cell Xenografts and Stromal Cells

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2016-02-17 | PXD001778 | Pride

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