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  • 1
    Online Resource
    Online Resource
    A Novel Function of Interleukin‐10 Promoting Self‐Renewal of Hematopoietic Stem Cells
    Oxford University Press (OUP) ; 2007
    In:  STEM CELLS Vol. 25, No. 7 ( 2007-07), p. 1814-1822
    Details
    In: STEM CELLS, Oxford University Press (OUP), Vol. 25, No. 7 ( 2007-07), p. 1814-1822
    Type of Medium: Online Resource
    ISSN: 1066-5099 , 1549-4918
    URL: Article
    DOI: 10.1634/stemcells.2007-0002
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2007
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    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Differential modulation of Myb family genes by Ets-2
    Springer Science and Business Media LLC ; 2004
    In:  Oncogene Vol. 23, No. 23 ( 2004-05-20), p. 4177-4181
    Details
    In: Oncogene, Springer Science and Business Media LLC, Vol. 23, No. 23 ( 2004-05-20), p. 4177-4181
    Type of Medium: Online Resource
    ISSN: 0950-9232 , 1476-5594
    URL: Article
    DOI: 10.1038/sj.onc.1207537
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2004
    detail.hit.zdb_id: 2008404-3
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  • 3
    Online Resource
    Online Resource
    Identification of a Stroma-Mediated Wnt Signal Promoting Self-Renewal of Hematopoietic Stem Cells in the Stem Cell Niche.
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 2208-2208
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 2208-2208
    Abstract: With contrasting results recently reported on the effects of b-catenin on hematopoietic stem cells (HSCs), the precise role of Wnt on HSC regulation remains in question. Here, we show that Wnt-b-catenin signaling triggers distinct biological effects on HSCs depending on the target of activation within the hematopoietic microenvironment. Retroviral transduction of a stable form of b-catenin into HSCs caused a loss of competitive repopulating units (CRUs) in a limiting-dilution assay, whereas stabilized b-catenin in stromal cells CRU frequencies of co-cultured HSCs with higher preservation of undifferentiated state and caused enhanced levels of reconstitution in a manner dependent on direct contact between HSC and stroma. The enhancing effect of b-catenin stabilized stroma on HSC was also observed for human HSCs exhibiting higher frequencies of lympho-myeloid repopulating cells after transplantation into NOD/SCID mice. Interestingly, gene expression patterns of Wnt signaling molecules revealed compartmentalization in a manner that canonical Wnt ligands were preferentially expressed in the hematopoietic cells while molecules for reception of the signal such as Frizzled receptors or their co-receptors are preferentially expressed in stromal component, suggesting the role of stromal component as a target of Wnt signals in the niche. Furthermore, b-catenin accumulated selectively in the endosteal stroma of the trabecule region in “stressed” marrows, but not in “steady-state” marrows. Taken together, these results suggest stroma-mediated Wnt signals may function as microenvironmental cues for HSC self-renewal in the stem cell niche.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.2208.2208
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 4
    Online Resource
    Online Resource
    IL10-Transduced Mesenchymal Stem Cells Attenuate Experimental Acute Graft-Versus-Host Disease.
    American Society of Hematology ; 2005
    In:  Blood Vol. 106, No. 11 ( 2005-11-16), p. 5247-5247
    Details
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 5247-5247
    Abstract: Recent data suggest that, due to their immunosuppressive nature, adult mesenchymal stem cells (MSCs) may be of interest to enhance allogeneic hematopoietic engraftment and prevent graft-versus-host disease (GVHD). Using a murine model of acute GVHD, this study investigated whether the immunosuppressive properties of MSCs could reduce the severity of experimental GVHD. In a MHC-mismatched C57BL/6→B6D2F1 model, recipient animals were transplanted with bone marrow (BM) cells (10x106) plus 20x106 splenocytes after 1100 cGy on day 0. Various doses (1~3x106) of donor BM-derived MSCs were given intravenously from day 1 to day 5 and subsequently evaluated the clinical and immunologic parameters. MSCs did not attenuate the severity of acute GVHD. Using GFP expressing MSCs, we were unable to detect labeled cells in liver, spleen, lymph nodes and lung day 7 post-BMT. Because MSCs fail to display any immunosuppression in this experimental GVHD model and induce an immunosuppressive microenvironment through the production of IL10, we investigated whether the use of genetically modified MSCs expressing IL10 (IL10-transduced MSCs, IL10 MSCs) could improve the GVHD protection. Lethally irradiated recipients were transplanted and injected with 2x106 IL10 MSCs, MSC expressing MIG as a vector (MIG MSCs), or diluent on day 1. Compared with MIG MSCs or controls, recipients of IL10 MSCs demonstrated significantly reduced mortality at day 50 after BMT (percent survival, 0% or 10% vs 70%, P & lt;0.001). The reduction in mortality was confirmed by the semi-quantitative GVHD score (P & lt;0.01). It was associated with decreased serum levels of pro-inflammatory cytokines, IFNγ on day 7 (IL10 MSCs vs MIG MSCs; 297±116 pg/ml vs 681±87 pg/ml, P=0.015). Serum levels of TNFα or splenic donor CD3+ cell numbers were not different between the groups. Thus, benefical effects on GVHD could be observed when MSCs were engineered to express an anti-inflammatory cytokine, IL10. The mechanisms for the GVHD protection effect of IL10 MSCs in this murine model are currently under investigation.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V106.11.5247.5247
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
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    detail.hit.zdb_id: 80069-7
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  • 5
    Online Resource
    Online Resource
    Identification of a Stroma-Mediated Wnt/β-Catenin Signal Promoting Self-Renewal of Hematopoietic Stem Cells in the Stem Cell Niche
    Oxford University Press (OUP) ; 2009
    In:  Stem Cells Vol. 27, No. 6 ( 2009-06-01), p. 1318-1329
    Details
    In: Stem Cells, Oxford University Press (OUP), Vol. 27, No. 6 ( 2009-06-01), p. 1318-1329
    Abstract: With contrasting observations on the effects of β-catenin on hematopoietic stem cells (HSCs), the precise role of Wnt/β-catenin signals on HSC regulation remains unclear. Here, we show a distinct mode of Wnt/β-catenin signal that can regulate HSCs in a stroma-dependent manner. Stabilization of β-catenin in the bone marrow stromal cells promoted maintenance and self-renewal of HSCs in a contact-dependent manner, whereas direct stabilization in hematopoietic cells caused loss of HSCs. Interestingly, canonical Wnt receptors and β-catenin accumulation were predominantly enriched in the stromal rather than the hematopoietic compartment of bone marrows. Moreover, the active form of β-catenin accumulated selectively in the trabecular endosteum in “Wnt 3a-stimulated” or “irradiation-stressed,” but not in “steady-state” marrows. Notably, notch ligands were induced in Wnt/β-catenin activated bone marrow stroma and downstream notch signal activation was seen in the HSCs in contact with the activated stroma. Taken together, Wnt/β-catenin activated stroma and their cross-talk with HSCs may function as a physiologically regulated microenvironmental cue for HSC self-renewal in the stem cell niche. Disclosure of potential conflicts of interest is found at the end of this article.
    Type of Medium: Online Resource
    ISSN: 1066-5099 , 1549-4918
    URL: Article
    DOI: 10.1002/stem.52
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2009
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    SSG: 12
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  • 6
    Online Resource
    Online Resource
    High Level CD24 Expression Is Correlated to Higher Metastatic Potential of Breast Cancer Cells.
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 2859-2859
    Details
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 2859-2859
    Abstract: Cancer stem cells are subpopulations of cancer cells with potential to seed and develop new cancer mass causing recurrence and/or metastasis, but phenotypic characteristics of such cell populations remains uncertain. As an initial approach to identify heterogeneity in cancer mass, we performed comparative study using matched pairs of primary breast cancer masses and their immediate metastatic counterparts in regional LN. First, in the gene expression study of primary tumor mass and their LN counterpart using cDNA microarray, about 100 genes showed differential expression between the two, but with variations depending on cases (3 Exp). In addition, when fresh individually matched surgical block from primary mass and LN mass were each inoculated into NOD/SCID mice, higher growth of LN-derived mass was observed supporting distinction between the two (2 Exp). In subsequent search for phenotypic difference between the two, 99 primary-LN tissue pairs with individual matching were immunostained for CD24, a newly proposed marker for cancer stem cell, and analysed by semiquantitative scoring (0, 1+, 2+, 3+, 4+). Among 73 cases with positive staining for CD24, higher level of CD24 expression in LN mass compared to its matched primary tumor tissue was observed in 38 cases (52.1%), while the opposite was for only 7 cases (9.6%). Furthermore, high level expression (4+) of CD24 was observed more frequently in LN tumor tissues (63.0%, 46/73) than in their primary tumor counterparts (26%, 19/73)( P = 0.000). These results support the notion that cancer cells in tumor mass are clonally heterogeneous and suggest that CD24 expression could be related to characteristic of metastatic cancer stem cells.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.2859.2859
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
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    detail.hit.zdb_id: 80069-7
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  • 7
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    Online Resource
    Stromal Interaction of Lymphoma Cells Regulates Survival and Chemoresistance
    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 21 ( 2011-11-18), p. 5195-5195
    Details
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 5195-5195
    Abstract: Abstract 5195 High-grade lymphomas are aggressive but largely curable, whereas low-grade lymphomas are indolent, but frequently recur to be incurable, paradoxically. Mesenchymal stromal cells (MSCs) have been known to participate for reconstituting microenvironment. Studies show that signalings between normal lymphoid cells and stromal cells were frequently altered in high grade lymphomas, but relatively conserved in low grade lymphomas. However, which cell and mechanism is responsible for lymphoma recurrence remains unclear. Here we hypothesized that the interaction with stroma may play a role for lymphoma cell growth and survival. For this, we investigated the effect of MSCs on lymphoma cell growth and chemo-resistance by using a coculture system with MSCs (derived from tonsil), as a stromal microenvironment for lymphoma cells. First, coculture of lymphoma cell line (Pfeiffer) and primary lymphoma cells with/without MSCs for 3 days showed that the MSC-cocultured cells grew more rapidly (1.4 times and 1.8 times for Pfeiffer and primary cells, respectively) than MSC-free lymphoma cells. To further investigate the underlying mechanism of promoting growth, lymphoma cells were cocultured with MSCs in the presence or absence of transwell filter. At day 4, the proliferation of lymphoma cells in the absence of transwell was 3.5 times higher than in the presence of transwell. Interestingly, the lymphoma cells cocultured with MSCs showed increased expression of CXCR4 compared with lymphoma cells cultured alone. When the cyto-protective effect of MSCs was examined by doxorubicin treatment (1ug/ml) in the presence or absence of MSCs, 91% of MSC-cocultured cells survived, whereas only 28% of stroma-free cultured cells survived. These results demonstrate that the direct contact interaction with stroma might be important for lymphoma cell growth and survival. In conclusion, our data suggest that the interaction with stromal microenvironment is an important factor for survival of lymphoma cells which cells might be responsible for chemoresistance, and raise the possibility that the stromal interaction could be a potential target for lymphoma treatment. Disclosures: No relevant conflicts of interest to declare. This research was supported by a grant (10172KFDA993) from Korea Food & Drug Administration in 2011. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V118.21.5195.5195
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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    detail.hit.zdb_id: 80069-7
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  • 8
    Online Resource
    Online Resource
    Shift of EMT gradient in 3D spheroid MSCs for activation of mesenchymal niche function
    Springer Science and Business Media LLC ; 2017
    In:  Scientific Reports Vol. 7, No. 1 ( 2017-07-31)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-07-31)
    Abstract: Despite the wide use of mesenchymal stromal cells (MSCs) for paracrine support in clinical trials, their variable and heterogeneous supporting activity pose major challenges. While three-dimensional (3D) MSC cultures are emerging as alternative approaches, key changes in cellular characteristics during 3D-spheroid formation remain unclear. Here, we show that MSCs in 3D spheroids undergo further progression towards the epithelial-mesenchymal transition (EMT), driven by upregulation of EMT-promoting microRNAs and suppression of EMT-inhibitory miRNAs. The shift of EMT in MSCs is associated with widespread histone modifications mimicking the epigenetic reprogramming towards enhanced chromatin dynamics and stem cell-like properties, but without changes in their surface phenotype. Notably, these molecular shifts towards EMT in 3D MSCs caused enhanced stem cell niche activity, resulting in higher stimulation of hematopoietic progenitor self-renewal and cancer stem cell metastasis. Moreover, miRNA-mediated induction of EMT in 2D MSCs were sufficient to mimic the enhanced niche activity of 3D spheroid MSCs. Thus, the molecular hierarchy in the EMT gradient among phenotypically indistinguishable MSCs revealed the previously unrecognized functional parameters in MSCs, and the EMT-enhanced “naïve” mesenchymal state represents an ‘activated mesenchymal niche’ in 3D spheroid MSCs.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-017-07049-3
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2615211-3
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  • 9
    Online Resource
    Online Resource
    Intramarrow injection of β-catenin-activated, but not naïve mesenchymal stromal cells stimulates self-renewal of hematopoietic stem cells in bone marrow
    Springer Science and Business Media LLC ; 2010
    In:  Experimental and Molecular Medicine Vol. 42, No. 2 ( 2010), p. 122-
    Details
    In: Experimental and Molecular Medicine, Springer Science and Business Media LLC, Vol. 42, No. 2 ( 2010), p. 122-
    Type of Medium: Online Resource
    ISSN: 1226-3613
    URL: Article
    DOI: 10.3858/emm.2010.42.2.014
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2010
    detail.hit.zdb_id: 2084833-X
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