Dataset Information

Increased Haematopoietic Supportive Function of USSC from Umbilical Cord Blood Compared to CB MSC and Possible Role of DLK-1.

ABSTRACT: Multipotent stromal cells can be isolated from a variety of different tissues in the body. In contrast to stromal cells from the adult bone marrow (BM) or adipose tissue, cord blood (CB) multipotent stromal cells (MSC) are biologically younger. Since first being described by our group, delta like 1 homologue (DLK-1) was determined as a discriminating factor between the distinct cord blood-derived subpopulations: the unrestricted somatic stromal cells (USSC), which lack adipogenic differentiation capacity, and the BM MSC-like CB MSC. In this study, experiments assessing the haematopoiesis-supporting capacity and molecular biological analyses were conducted and clearly confirmed different properties. Compared to CB MSC, USSC lead to a higher expansion of haematopoietic cells and in addition express significantly higher levels of insulin-like growth factor binding protein 1 (IGFBP1), but lower levels of IGF2. The data presented here also indicate that DLK-1 might not be the sole factor responsible for the inhibition of adipogenic differentiation potential in USSC but nevertheless indicates a biological diversity among cord blood-derived stromal cells.

SUBMITTER: Kluth SM

PROVIDER: S-EPMC3649714 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Increased Haematopoietic Supportive Function of USSC from Umbilical Cord Blood Compared to CB MSC and Possible Role of DLK-1.

Kluth Simone Maria SM Radke Teja Falk TF Kögler Gesine G

Stem cells international 20130403

Multipotent stromal cells can be isolated from a variety of different tissues in the body. In contrast to stromal cells from the adult bone marrow (BM) or adipose tissue, cord blood (CB) multipotent stromal cells (MSC) are biologically younger. Since first being described by our group, delta like 1 homologue (DLK-1) was determined as a discriminating factor between the distinct cord blood-derived subpopulations: the unrestricted somatic stromal cells (USSC), which lack adipogenic differentiation ...[more]

PMID: 23690788

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Project description:BACKGROUND:The therapeutic role of mesenchymal stem cells (MSCs) has been widely confirmed in several animal models of premature infant diseases. Micromolecule peptides have shown promise for the treatment of premature infant diseases. However, the potential role of peptides secreted from MSCs has not been studied. The purpose of this study is to help to broaden the knowledge of the hUC-MSC secretome at the peptide level through peptidomic profile analysis. METHODS:We used tandem mass tag (TMT) labeling technology followed by tandem mass spectrometry to compare the peptidomic profile of preterm and term umbilical cord MSC (hUC-MSC) conditioned medium (CM). Gene Ontology (GO) enrichment analysis and ingenuity pathway analysis (IPA) were conducted to explore the differentially expressed peptides by predicting the functions of their precursor proteins. To evaluate the effect of candidate peptides on human lung epithelial cells stimulated by hydrogen peroxide (H2O2), quantitative real-time PCR (qRT-PCR), western blot analysis, and enzyme-linked immunosorbent assay (ELISA) were, respectively, adopted to detect inflammatory cytokines (TNF-?, IL-1?, and IL-6) expression levels at the mRNA and protein levels. RESULTS:A total of 131 peptides derived from 106 precursor proteins were differentially expressed in the preterm hUC-MSC CM compared with the term group, comprising 37 upregulated peptides and 94 downregulated peptides. Bioinformatics analysis showed that these differentially expressed peptides may be associated with developmental disorders, inflammatory response, and organismal injury. We also found that peptides 7118TGAKIKLVGT7127 derived from MUC19 and 508AAAAGPANVH517 derived from SIX5 reduced the expression levels of TNF-?, IL-1?, and IL-6 in H2O2-treated human lung epithelial cells. CONCLUSIONS:In summary, this study provides further secretomics information on hUC-MSCs and provides a series of peptides that might have antiinflammatory effects on pulmonary epithelial cells and contribute to the prevention and treatment of respiratory diseases in premature infants.

Project description:BackgroundMesenchymal stromal cells (MSC) possess immunomodulatory properties and low immunogenicity, both crucial properties for their development into an effective cellular immunotherapy. They have shown benefit in clinical trials targeting liver diseases; however the efficacy of MSC therapy will benefit from improvement of the immunomodulatory and immunogenic properties of MSC.MethodsMSC derived from human umbilical cords (ucMSC) were treated for 3 days in vitro with various inflammatory factors, interleukins, vitamins and serum deprivation. Their immunogenicity and immunomodulatory capacity were examined by gene-expression analysis, surface-marker expressions, IDO activity, PGE2 secretion and inhibition of T cell proliferation and IFNγ production. Furthermore, their activation of NK cell cytotoxicity was investigated via CD107a expression on NK cells. The immunomodulatory capacity, biodistribution and survival of pre-treated ucMSC were investigated in a CCl4-induced liver disease mouse model. In addition, capacity of pre-treated MSC to ameliorate liver inflammation was examined in an ex vivo liver inflammation co-culture model.ResultsIFN-γ and a multiple cytokine cocktail (MC) consisting of IFN-γ, TGFβ and retinoic acid upregulated the expression of immunomodulatory factor PD-L1 and IDO activity. Subsequently, both treatments enhanced the capacity of ucMSC to inhibit CD4 and CD8 T cell proliferation and IFN-γ production. The susceptibility of ucMSC for NK cell lysis was decreased by IFN-β, TGFβ and MC treatment. In vivo, no immunomodulation was observed by the ucMSC. Four hours after intravenous infusion in mice with CCl4-induced inflammatory liver injury, the majority of ucMSC were trapped in the lungs. Rapid clearance of ucMSC(VitB6), ucMSC(Starv + VitB6) and ucMSC(MC) and altered bio-distribution of ucMSC(TGFβ) compared to untreated ucMSC was observed. In the ex vivo co-culture system with inflammatory liver slices ucMSC(MC) showed significantly enhanced modulatory capacity compared to untreated ucMSC.ConclusionsThe present study demonstrates the responsiveness of ucMSC to in vitro optimisation treatment. The observed improvements in immunomodulatory capacity as well as immunogenicity after MC treatment may improve the efficacy of ucMSC as immunotherapy targeted towards liver inflammation.

Dataset Information

Increased Haematopoietic Supportive Function of USSC from Umbilical Cord Blood Compared to CB MSC and Possible Role of DLK-1.

Publications

Increased Haematopoietic Supportive Function of USSC from Umbilical Cord Blood Compared to CB MSC and Possible Role of DLK-1.

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