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Epigenetic and in vivo comparison of diverse mesenchymal stromal cell sources reveals an endochonrdal signature for human hematopoietic niche formation

ABSTRACT: Despite similarities in morphology, phenotype and in vitro behavior, Mesenchymal Stromal Cells (MSC) form various tissue sources show striking differences in their in vivo potential to form bone, cartilage and hematopoietic support tissue. Comparing four commonly use MSC sources (bone marrow (BM), white adipose tissue (WAT), umbilical cord (UC) and skin) we found only bone marrow (BM)-derived MSCs capable of endochondral ossification and marrow attraction. To gain mechanistic insights explaining this differences we analyzed gene expression characteristics of MSC from all four tissue sources using Affymetrix Genechip Human Gene 2.0 ST Array.

ORGANISM(S): Homo sapiens

PROVIDER: GSE57151 | GEO | 2014/04/30

SECONDARY ACCESSION(S): PRJNA245789

REPOSITORIES: GEO

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Epigenetic and in vivo comparison of diverse mesenchymal stromal cell sources reveals an endochonrdal signature for human hematopoietic niche formation

Project description:Despite similarities in morphology, phenotype and in vitro behavior, Mesenchymal Stromal Cells (MSC) form various tissue sources show striking differences in their in vivo potential to form bone, cartilage and hematopoietic support tissue. Comparing four commonly use MSC sources (bone marrow (BM), white adipose tissue (WAT), umbilical cord (UC) and skin) we found only bone marrow (BM)-derived MSCs capable of endochondral ossification and marrow attraction. To gain mechanistic insights explaining this differences we analyzed gene expression characteristics of MSC from all four tissue sources using Affymetrix Genechip Human Gene 2.0 ST Array. MSCs from BM, WAT, UC and skin were isolated using plastic adherence. Cells were expanded in standard alpha-MEM supplemented with pooled human platelet lysate fully replacing fetal bovine serum. MSCs were subcutaneously implanted into immune-compromised mice to comparatively evaluate bone formation and subsequent bone marrow attraction. In parallel we have isolated RNA from all sources to analyze tissue source specific gene expression profile.

2014-04-30 | E-GEOD-57151 | biostudies-arrayexpress

Human bone and marrow niche formation by mesenchymal progenitors in vivo is predefined by an organotypic epigenetic signature

Project description:In this study, we have analyzed DNA methylation characteristics of human mesenchymal stem and progenitor cells (MSPCs) form different tissue sources including bone marrow (BM), white adipose tissue (WAT ), umbilical cord (UC) as well as dermal fibroblasts by using the HumanMethylation450K array. Cells able to form bone through endochondral ossification and attract bone marrow in an innovative in vivo model were compared to cells lacking these capacities. Interestingly only BM-derived MSPCs were capable of bone formation and marrow attraction. These features correlated with unique epigenetic characteristics potentially enabling BM-derived cells to undergo endochondral ossification.

2015-02-04 | GSE41933 | GEO

Human bone and marrow niche formation by mesenchymal progenitors in vivo is predefined by an organotypic epigenetic signature

2015-02-04 | E-GEOD-41933 | biostudies-arrayexpress

Quantitative proteomics analysis of different sources of hMSCs

Project description:Mesenchymal stem cells (MSCs) are an attractive therapeutic tool for tissue engineering and re-generative medicine due to their regenerative and trophic properties. The best-known and most widely used are bone marrow MSCs, but they are now being harvested and developed from a wide range of adult and perinatal tissues. MSCs from different sources are believed to have dif-ferent secretion potentials and production, which may influence their therapeutic effects. To prove it, we performed a quantitative proteomic analysis based on the TMT technique of MSCs from 3 different sources: wharton’s jelly (WJ), dental pulp (DP) and bone marrow (BM). Our analysis has focused on MSC biological properties of interest for tissue engineering. We identified a total of 611 human proteins differentially expressed. WJ-MSCs shown the greatest variation compared to the other sources. WJ produced more extra-cellular matrix (ECM) proteins and ECM-affiliated proteins and appeared to more able to modulate the inflammatory and immune response. BM-MSCs display enhanced differentiation and paracrine communication capabilities. DP-MSC appeared to promote exosome production. The results obtained confirm the existence of differences between WJ, DP and BM-MSC and the need to select the MSC origin according to the therapeutic objective sought.

2023-09-20 | PXD043912 | Pride

Single-cell RNA sequencing of mesenchymal stromal cells from primary donor-matched tissue sources reveals functional heterogeneity in immune activity and cell motility

Project description:The efficacy of mesenchymal stromal cell (MSC) therapy is thought to depend on the intrinsic heterogeneity of MSC cultures isolated from different tissue sources as well as individual MSCs isolated from the same tissue source, neither of which is well understood. The horse model, in contrast to human and mouse, allows for simultaneous sample collection from multiple tissues of the same animal, which circumvents the inter-donor variation in MSC cultures observed in other models. In the present study, we performed single-cell RNA sequencing (scRNA-seq) on primary equine MSCs that were collected from three donor-matched tissue sources; adipose tissue (AT), bone marrow (BM), and peripheral blood (PB). We observed both inter- and intra-source heterogeneity across the three sources of equine MSCs.

2020-12-08 | GSE156467 | GEO

The enhancer landscape predetermines the skeletal regeneration capacity of stromal cells [ATAC-seq]

Project description:Mesenchymal stromal cells (MSCs) derived from bone marrow (BM) have stronger potential for endochondral ossification compared to white adipose tissue (WAT)-MSCs, umbilical cord (UC)-MSCs, and skin fibroblasts (FB). We assessed uniquely accessible enhancers facilitating bone regeneration potential.

2023-04-03 | GSE182496 | GEO

The enhancer landscape predetermines the skeletal regeneration capacity of stromal cells [ChIP-seq]

Project description:Mesenchymal stromal cells (MSCs) derived from bone marrow (BM) have stronger potential for endochondral ossification compared to white adipose tissue (WAT)-MSCs, umbilical cord (UC)-MSCs, chondrocytes (CH) and skin fibroblasts (FB). We assessed active regulatory regions facilitating bone-regeneration potential.

2023-04-03 | GSE182495 | GEO

Evaluating the therapeutic potential of different sources of mesenchymal stem cells in acute respiratory distress syndrome

Project description:In different preclinical studies, different sources of MSCs derived from adipose tissue, bone marrow, placenta, umbilical cord have shown effectiveness in treating ARDS. However, their clinical translation has not been effective as demonstrated by variable outcomes from clinical trials. One reason for this could be the MSC source chosen for clinical translation as there is lack of study comparing the different sources of MSCs. In previous work, we performed a “head-to-head” comparison between different sources of MSCs and showed that each source had a unique genomic and proteomic “signature”. Hence, in this current study, we investigated the choice of MSC source best suited for therapy in an LPS-induced mouse model of ARDS. We compare the 3 most commonly used MSC sources: bone marrow derived-MSCs (BM-MSCs), adipose tissue derived-MSCs (AD-MSCs) and umbilical cord derived-MSCs (UC-MSCs) therapy in LPS-induced ARDS model where we did bulk RNA sequencing of the lungs to validate the efficacy of therapy in terms of different changes in gene label and different pathways involved.

2023-08-23 | GSE241186 | GEO

Investigation of bone marrow microenvironment-induced drug resistance in acute lymphoblastic leukemia (ALL)

Project description:Bulk RNA-seq of B-ALL cells cocultured with bone marrow-mesenchymal stem cells (BM-MSC) identified that B-ALL acquire epithelial-mesenchymal transition (EMT) properties by interacting with primary bone marrow-mesenchymal stem cells (BM-MSC) and scRNA-seq dissected the hybrid cluster of adherent B-ALL (Adh B-ALL) harboring B-ALL and BM-MSC features induced by EMT program

2022-05-31 | GSE200039 | GEO

Mesenchymal Stromal Cells Derived from Human Embryonic Stem Cells, Fetal Limb and Bone Marrow Share a Common Phenotype but are Transcriptionally and Biologically Different [I]

Project description:Mesenchymal stromal cells (MSCs) can be obtained from several sources and the significant differences in their properties, makes it crucial to investigate the differentiation potential of MSCs from different sources to determine the optimal source of MSCs. We investigated if this biological heterogeneity in MSCs from different sources results in different mechanisms for their differentiation. In this study, we compared the gene expression patterns of phenotypically defined MSCs derived from three ontogenically different sources: Embryonic stem cells (hES-MSCs), Fetal limb (Flb-MSCs) and Bone Marrow (BM-MSCs). Differentially expressed genes between differentiated cells and undifferentiated controls were compared across the three MSC sources. We found minimal overlap in differential gene expression (5-16%) among the three sources. Flb-MSCs were similar to BM-MSCs based on differential gene expression patterns. Pathway analysis of the differentially expressed genes using Ingenuity Pathway Analysis (IPA) revealed a large variation in the canonical pathways leading to MSC differentiation. The similar canonical pathways among the three sources were lineage specific. The Flb-MSCs showed maximum overlap of canonical pathways with the BM-MSCs, indicating that the Flb-MSCs is an intermediate source between the less specialised hES-MSC source and the more specialised BM-MSC source. The source specific pathways prove that MSCs from the three ontogenically different sources use different biological pathways to obtain similar differentiation outcomes. Thus our study advocates the understanding of biological pathways to obtain optimal sources of MSCs for various clinical applications.

2017-07-04 | GSE100748 | GEO

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