Dataset Information

Reconstruction and validation of a constraint-based metabolic network model for bone marrow-derived mesenchymal stem cells.

ABSTRACT:

Objectives

Over recent years, constraint-based modelling of metabolic networks has become increasingly popular; the models are suitable for system-level modelling of cell physiology. The goal of the present work was to reconstruct a constraint-based metabolic network model of bone marrow-derived mesenchymal stem cells (BMMSCs).

Materials and methods

To reconstruct a BMMSC-specific metabolic model, transcriptomic data of BMMSCs, and additionally, the human generic metabolic network model (Recon1) were used. Then, using the mCADRE algorithm, a draft metabolic network was reconstructed. Literature and proteomic data were subsequently used to refine and improve the draft. From this, iMSC1255 was derived to be the metabolic network model of BMMSCs.

Results

iMSC1255 has 1255 genes, 1850 metabolites and 2288 reactions. After including additional constraints based on previously reported experimental results, our model successfully predicted BMMSC growth rate and metabolic phenotypes.

Conclusions

Here, iMSC1255 is introduced to be the metabolic network model of bone marrow-derived mesenchymal stem cells. Based on current knowledge, this is the first report on genome-scale reconstruction and validation of a stem cell metabolic network model.

SUBMITTER: Fouladiha H

PROVIDER: S-EPMC6496242 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Publications

Reconstruction and validation of a constraint-based metabolic network model for bone marrow-derived mesenchymal stem cells.

Fouladiha H H Marashi S-A SA Shokrgozar M A MA

Cell proliferation 20150701 4

<h4>Objectives</h4>Over recent years, constraint-based modelling of metabolic networks has become increasingly popular; the models are suitable for system-level modelling of cell physiology. The goal of the present work was to reconstruct a constraint-based metabolic network model of bone marrow-derived mesenchymal stem cells (BMMSCs).<h4>Materials and methods</h4>To reconstruct a BMMSC-specific metabolic model, transcriptomic data of BMMSCs, and additionally, the human generic metabolic network ...[more]

PMID: 26132591

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Project description:Prostate cancer recurrence involves increased growth of cancer epithelial cells, as androgen dependent prostate cancer progresses to castrate resistant prostate cancer (CRPC) following initial therapy. Understanding CRPC prostate regrowth will provide opportunities for new cancer therapies to treat advanced disease.Elevated chemokine expression in the prostate stroma of a castrate resistant mouse model, Tgfbr2(fspKO), prompted us to look at the involvement of bone marrow derived cells (BMDCs) in prostate regrowth. We identified bone marrow cells recruited to the prostate in GFP-chimeric mice. A dramatic increase in BMDC recruitment for prostate regrowth occurred three days after exogenous testosterone implantation. Recruitment led to incorporation of BMDCs within the prostate epithelia. Immunofluorescence staining suggested BMDCs in the prostate coexpressed androgen receptor; p63, a basal epithelial marker; and cytokeratin 8, a luminal epithelial marker. A subset of the BMDC population, mesenchymal stem cells (MSCs), were specifically found to be incorporated in the prostate at its greatest time of remodeling. Rosa26 expressing MSCs injected into GFP mice supported MSC fusion with resident prostate epithelial cells through co-localization of β-galactosidase and GFP during regrowth. In a human C4-2B xenograft model of CRPC, MSCs were specifically recruited. Injection of GFP-labeled MSCs supported C4-2B tumor progression by potentiating canonical Wnt signaling. The use of MSCs as a targeted delivery vector for the exogenously expressed Wnt antagonist, secreted frizzled related protein-2 (SFRP2), reduced tumor growth, increased apoptosis and potentiated tumor necrosis.Mesenchymal stem cells fuse with prostate epithelia during the process of prostate regrowth. MSCs recruited to the regrowing prostate can be used as a vehicle for transporting genetic information with potential therapeutic effects on castrate resistant prostate cancer, for instance by antagonizing Wnt signaling through SFRP2.

Dataset Information

Reconstruction and validation of a constraint-based metabolic network model for bone marrow-derived mesenchymal stem cells.

Objectives

Materials and methods

Results

Conclusions

Publications

Reconstruction and validation of a constraint-based metabolic network model for bone marrow-derived mesenchymal stem cells.

Similar Datasets

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