Human Adipose Tissue-Derived Mesenchymal Stem Cells Target Brain Tumor-Initiating Cells
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Mendeley | Further Information

{"title"=>"Human Adipose Tissue-Derived Mesenchymal Stem Cells Target Brain Tumor-Initiating Cells", "type"=>"journal", "authors"=>[{"first_name"=>"Seung Ah", "last_name"=>"Choi"}, {"first_name"=>"Ji Yeoun", "last_name"=>"Lee"}, {"first_name"=>"Sung Eun", "last_name"=>"Kwon"}, {"first_name"=>"Kyu-Chang", "last_name"=>"Wang"}, {"first_name"=>"Ji Hoon", "last_name"=>"Phi"}, {"first_name"=>"Jung Won", "last_name"=>"Choi"}, {"first_name"=>"Xiong", "last_name"=>"Jin"}, {"first_name"=>"Ja Yun", "last_name"=>"Lim"}, {"first_name"=>"Hyunggee", "last_name"=>"Kim"}, {"first_name"=>"Seung-Ki", "last_name"=>"Kim"}], "year"=>2015, "source"=>"PLOS ONE", "identifiers"=>{"pmid"=>"26076490", "doi"=>"10.1371/journal.pone.0129292", "issn"=>"1932-6203"}, "id"=>"1799b13e-daa9-3b9e-b988-dacad4d62d54", "abstract"=>"In neuro-oncology, the biology of neural stem cells (NSCs) has been pursued in two ways: as tumor-initiating cells (TICs) and as a potential cell-based vehicle for gene therapy. NSCs as well as mesenchymal stem cells (MSCs) have been reported to possess tumor tropism capacities. However, there is little data on the migratory capacity of MSCs toward brain tumor-initiating cells (BTICs). This study focuses on the ability of human adipose tissue derived MSCs (hAT-MSCs) to target BTICs and their crosstalk in the microenvironment. BTICs were isolated from three different types of brain tumors. The migration capacities of hAT-MSCs toward BTICs were examined using an in vitro migration assay and in vivo bioluminescence imaging analysis. To investigate the crosstalk between hAT-MSCs and BTICs, we analyzed the mRNA expression patterns of cyto-chemokine receptors by RT-qPCR and the protein level of their ligands in co-cultured medium. The candidate cyto-chemokine receptors were selectively inhibited using siRNAs. Both in vitro and in vivo experiments showed that hAT-MSCs possess migratory abilities to target BTICs isolated from medulloblastoma, atypical teratoid/rhabdoid tumors (AT/RT) and glioblastoma. Different types of cyto-chemokines are involved in the crosstalk between hAT-MSCs and BTICs (medulloblastoma and AT/RT: CXCR4/SDF-1, CCR5/RANTES, IL6R/IL-6 and IL8R/IL8; glioblastoma: CXCR4/SDF-1, IL6R/IL-6, IL8R/IL-8 and IGF1R/IGF-1). Our findings demonstrated the migratory ability of hAT-MSCs for BTICs, implying the potential use of MSCs as a delivery vehicle for gene therapy. This study also confirmed the expression of hAT-MSCs cytokine receptors and the BTIC ligands that play roles in their crosstalk.", "link"=>"http://www.mendeley.com/research/human-adipose-tissuederived-mesenchymal-stem-cells-target-brain-tumorinitiating-cells-2", "reader_count"=>25, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Student > Doctoral Student"=>3, "Researcher"=>6, "Student > Ph. D. Student"=>8, "Student > Master"=>2, "Other"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Student > Doctoral Student"=>3, "Researcher"=>6, "Student > Ph. D. Student"=>8, "Student > Master"=>2, "Other"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>6, "Engineering"=>2, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>9, "Medicine and Dentistry"=>3, "Psychology"=>2, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Psychology"=>{"Psychology"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>6}}, "reader_count_by_country"=>{"United Kingdom"=>1}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2114492"], "description"=>"<p>(A) Tumor spheres show BTIC characteristics. Confocal microscopic analysis of tumor spheres stained with nestin and musashi. Scale bar, 50 μm. (B) The gross appearance of tumor formation in the nude mouse brain after injection of BTICs; ×1.25 magnification. (C) Flow cytometry analysis shows the immunophenotyping of cultured hAT-MSCs. hAT-MSCs are stained positive for CD73, CD90 and CD105 but negative for CD31, CD34 and CD45. Histograms represent the relative number of cells versus fluorescent intensity. (D) hAT-MSCs were differentiated into adipocyte, osteocyte and chondrocyte cells. Neutral lipid vacuoles are indicated by adipogenesis staining by Oil Red O. The accumulation of alkaline phosphatase and calcium oxalates, shown by Alizarin Red staining, demonstrates differentiation into the osteoblast lineage. Chondrogenic differentiation is indicated by Alcian blue staining to detect type II collagen. Scale bar, 100 μm.</p>", "links"=>[], "tags"=>["crosstalk", "target BTICs", "ccr", "igf", "IL 8R glioblastoma", "mRNA expression patterns", "1r", "cxcr", "tumor tropism capacities", "6r", "vivo bioluminescence imaging analysis", "Gene therapy", "msc", "nsc"], "article_id"=>1450573, "categories"=>["Biological Sciences"], "users"=>["Seung Ah Choi", "Ji Yeoun Lee", "Sung Eun Kwon", "Kyu-Chang Wang", "Ji Hoon Phi", "Jung Won Choi", "Xiong Jin", "Ja Yun Lim", "Hyunggee Kim", "Seung-Ki Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0129292.g001", "stats"=>{"downloads"=>5, "page_views"=>32, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characterization_of_brain_tumor_initiating_cells_BTICs_and_human_adipose_tissue_derived_mesenchymal_stem_cells_hAT_MSCs_/1450573", "title"=>"Characterization of brain tumor-initiating cells (BTICs) and human adipose tissue-derived mesenchymal stem cells (hAT-MSCs).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-15 04:37:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/2114494"], "description"=>"<p>(A) The migration ability of hAT-MSCs was assessed and compared with that of HFF1 cells. Representative images of stained filters show migrated hAT-MSCs toward medulloblastoma-BTICs, atypical teratoid/rhabdoid tumors (AT/RT)-BTICs and glioblastoma-BTICs. hAT-MSCs exhibited greater migratory abilities toward BTICs compared with HFF1 cells and hAT-MSCs did not migrate toward HFF1; ×40 magnification. (B) Migration was quantified based on the OD value after dissolving the stained cells. The data shown are averages of quadruplicate wells, and bars represent ± SD. ***Significant difference from control (P < 0.001).</p>", "links"=>[], "tags"=>["crosstalk", "target BTICs", "ccr", "igf", "IL 8R glioblastoma", "mRNA expression patterns", "1r", "cxcr", "tumor tropism capacities", "6r", "vivo bioluminescence imaging analysis", "Gene therapy", "msc", "nsc"], "article_id"=>1450575, "categories"=>["Biological Sciences"], "users"=>["Seung Ah Choi", "Ji Yeoun Lee", "Sung Eun Kwon", "Kyu-Chang Wang", "Ji Hoon Phi", "Jung Won Choi", "Xiong Jin", "Ja Yun Lim", "Hyunggee Kim", "Seung-Ki Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0129292.g002", "stats"=>{"downloads"=>3, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Migratory_ability_of_human_adipose_tissue_derived_mesenchymal_stem_cells_hAT_MSCs_toward_brain_tumor_initiating_cells_BTICs_in_vitro_/1450575", "title"=>"Migratory ability of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) toward brain tumor-initiating cells (BTICs) <i>in vitro</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-15 04:37:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/2114495"], "description"=>"<p>Fluorescence images of the brains were taken at the indicated times. (A) In the absence of tumor, the fluorescent signals of hAT-MSCs (blue) are weakened at 2 weeks and are not detectable at 3 weeks. (B) <i>In vivo</i> sequential tracking was performed by injecting both NEO-LIVE 675-labeled BTICs (red) and NEO-LIVE 797-labeled hAT-MSCs (blue). hAT-MSCs gradually migrate toward the tumor site, and strong fluorescent signals are observed at 4 weeks post-injection at the tumor site. (C) Mice were injected the NEO-LIVE 797-labeled hAT-MSCs or HFF1. Representative <i>in vivo</i> fluorescence images show that the HFF1 signals are decreased or fade out. (D) On the contrary, the hAT-MSC signals are widened at all BTIC-derived mouse brain tumor sites at 3 weeks post-injection when compared with HFF1 cells. The color bar indicates radiant efficiency.</p>", "links"=>[], "tags"=>["crosstalk", "target BTICs", "ccr", "igf", "IL 8R glioblastoma", "mRNA expression patterns", "1r", "cxcr", "tumor tropism capacities", "6r", "vivo bioluminescence imaging analysis", "Gene therapy", "msc", "nsc"], "article_id"=>1450576, "categories"=>["Biological Sciences"], "users"=>["Seung Ah Choi", "Ji Yeoun Lee", "Sung Eun Kwon", "Kyu-Chang Wang", "Ji Hoon Phi", "Jung Won Choi", "Xiong Jin", "Ja Yun Lim", "Hyunggee Kim", "Seung-Ki Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0129292.g003", "stats"=>{"downloads"=>3, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Migratory_ability_of_human_adipose_tissue_derived_mesenchymal_stem_cells_hAT_MSCs_toward_brain_tumor_initiating_cells_BTICs_in_vivo_/1450576", "title"=>"Migratory ability of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) toward brain tumor-initiating cells (BTICs) <i>in vivo</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-15 04:37:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/2114496"], "description"=>"<p>Real-time Quantitative Polymerase Chain Reaction (RT-qPCR) analysis of cyto-chemokine receptors after co-culture of (A) medulloblastoma-BTICs, (B) atypical teratoid/rhabdoid tumors (AT/RT)-BTICs and (C) glioblastoma-BTICs. The mRNA level of each cytokine receptor was normalized to the level of GAPDH. All data are representative of three independent experiments, and each value represents the mean ± SD. *Significant difference from control (P < 0.05).</p>", "links"=>[], "tags"=>["crosstalk", "target BTICs", "ccr", "igf", "IL 8R glioblastoma", "mRNA expression patterns", "1r", "cxcr", "tumor tropism capacities", "6r", "vivo bioluminescence imaging analysis", "Gene therapy", "msc", "nsc"], "article_id"=>1450577, "categories"=>["Biological Sciences"], "users"=>["Seung Ah Choi", "Ji Yeoun Lee", "Sung Eun Kwon", "Kyu-Chang Wang", "Ji Hoon Phi", "Jung Won Choi", "Xiong Jin", "Ja Yun Lim", "Hyunggee Kim", "Seung-Ki Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0129292.g004", "stats"=>{"downloads"=>8, "page_views"=>68, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_mRNA_expression_of_cyto_chemokine_receptors_in_human_adipose_tissue_derived_mesenchymal_stem_cells_hAT_MSCs_after_co_culture_with_brain_tumor_initiating_cells_BTICs_/1450577", "title"=>"mRNA expression of cyto-chemokine receptors in human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) after co-culture with brain tumor-initiating cells (BTICs).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-15 04:37:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/2114497"], "description"=>"<p>Western blot analysis shows the increased expression of SDF-1 and decreased expression of IL-8 in all BTICs co-cultured with hAT-MSCs. (A and B) In medulloblastoma-BTICs and atypical teratoid/rhabdoid tumors (AT/RT)-BTICs, the expression of RANTES is increased, but that of IL-8 is not changed. (C) In glioblastoma-BTICs co-cultured with hAT-MSCs, the expression of IGF-1 is higher but that of IL-6 is lower. All data are representative of three independent experiments.</p>", "links"=>[], "tags"=>["crosstalk", "target BTICs", "ccr", "igf", "IL 8R glioblastoma", "mRNA expression patterns", "1r", "cxcr", "tumor tropism capacities", "6r", "vivo bioluminescence imaging analysis", "Gene therapy", "msc", "nsc"], "article_id"=>1450578, "categories"=>["Biological Sciences"], "users"=>["Seung Ah Choi", "Ji Yeoun Lee", "Sung Eun Kwon", "Kyu-Chang Wang", "Ji Hoon Phi", "Jung Won Choi", "Xiong Jin", "Ja Yun Lim", "Hyunggee Kim", "Seung-Ki Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0129292.g005", "stats"=>{"downloads"=>1, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cyto_chemokine_ligand_protein_expression_in_brain_tumor_initiating_cells_BTICs_after_co_culture_with_human_adipose_tissue_derived_mesenchymal_stem_cells_hAT_MSCs_or_HFF1_cells_/1450578", "title"=>"Cyto-chemokine ligand protein expression in brain tumor-initiating cells (BTICs) after co-culture with human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) or HFF1 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-15 04:37:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/2114498"], "description"=>"<p>After siRNAs treatment to each cytokine receptors on hAT-MSCs, (A) the protein expressions were confirmed in hAT-MSCs by western blot and (B) the migratory ability toward BTICs is assessed using trans-well assay. (C) The quantified results show inhibition of migration by selective knock down of cytokine receptors. ×50 magnification. All data are representative of three independent experiments, and each value represents the mean ± SD. *P < 0.05, **P < 0.01, ***P < 0.001.</p>", "links"=>[], "tags"=>["crosstalk", "target BTICs", "ccr", "igf", "IL 8R glioblastoma", "mRNA expression patterns", "1r", "cxcr", "tumor tropism capacities", "6r", "vivo bioluminescence imaging analysis", "Gene therapy", "msc", "nsc"], "article_id"=>1450579, "categories"=>["Biological Sciences"], "users"=>["Seung Ah Choi", "Ji Yeoun Lee", "Sung Eun Kwon", "Kyu-Chang Wang", "Ji Hoon Phi", "Jung Won Choi", "Xiong Jin", "Ja Yun Lim", "Hyunggee Kim", "Seung-Ki Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0129292.g006", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Knock_down_of_cytokine_receptors_on_hAT_MSCs_/1450579", "title"=>"Knock down of cytokine receptors on hAT-MSCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-15 04:37:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/2114499"], "description"=>"<p>BTICs: brain tumor initiating cells, HFF1: human foreskin fibroblast, hAT-MSCs: human adipose-derived mesenchymal stem cells, AT/RT: atypical teratoid rhabdoid tumor, MCP-1: monocyte chemoattractant protein 1, SDF-1: stromal cell-derived factor 1, RANTES: regulated on activation, normal T cell expressed and secreted, IL-6: interleukin-6 ligand, IL-8: interleukin-8, IGF-1: insulin-like growth factor 1ligand, PDGF-bb: platelet-derived growth factor, VEGF: vascular endothelial growth factor, Ang-1: angiopoietin1</p><p>*[induced cytokine level in the BTICs with HFF1] = [total cytokine level in the BTICs with HFF1]-[cytokine level in the HFF1 only]</p><p>[induced cytokine level in the BTICs with hAT-MSCs] = [total cytokine level in the BTICs with hAT-MSCs]-[cytokine level in the hAT-MSCs only]</p><p>Induced cytokine levels in the BTICs after co-cultured with HFF1 or hAT-MSCs (pg/ml)<sup><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0129292#t001fn002\" target=\"_blank\">*</a></sup>.</p>", "links"=>[], "tags"=>["crosstalk", "target BTICs", "ccr", "igf", "IL 8R glioblastoma", "mRNA expression patterns", "1r", "cxcr", "tumor tropism capacities", "6r", "vivo bioluminescence imaging analysis", "Gene therapy", "msc", "nsc"], "article_id"=>1450580, "categories"=>["Biological Sciences"], "users"=>["Seung Ah Choi", "Ji Yeoun Lee", "Sung Eun Kwon", "Kyu-Chang Wang", "Ji Hoon Phi", "Jung Won Choi", "Xiong Jin", "Ja Yun Lim", "Hyunggee Kim", "Seung-Ki Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0129292.t001", "stats"=>{"downloads"=>9, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Induced_cytokine_levels_in_the_BTICs_after_co_cultured_with_HFF1_or_hAT_MSCs_pg_ml_/1450580", "title"=>"Induced cytokine levels in the BTICs after co-cultured with HFF1 or hAT-MSCs (pg/ml)<sup>*</sup>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-06-15 04:37:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/2114505", "https://ndownloader.figshare.com/files/2114506", "https://ndownloader.figshare.com/files/2114507", "https://ndownloader.figshare.com/files/2114509", "https://ndownloader.figshare.com/files/2114510"], "description"=>"<div><p>In neuro-oncology, the biology of neural stem cells (NSCs) has been pursued in two ways: as tumor-initiating cells (TICs) and as a potential cell-based vehicle for gene therapy. NSCs as well as mesenchymal stem cells (MSCs) have been reported to possess tumor tropism capacities. However, there is little data on the migratory capacity of MSCs toward brain tumor-initiating cells (BTICs). This study focuses on the ability of human adipose tissue derived MSCs (hAT-MSCs) to target BTICs and their crosstalk in the microenvironment. BTICs were isolated from three different types of brain tumors. The migration capacities of hAT-MSCs toward BTICs were examined using an <i>in vitro</i> migration assay and <i>in vivo</i> bioluminescence imaging analysis. To investigate the crosstalk between hAT-MSCs and BTICs, we analyzed the mRNA expression patterns of cyto-chemokine receptors by RT-qPCR and the protein level of their ligands in co-cultured medium. The candidate cyto-chemokine receptors were selectively inhibited using siRNAs. Both <i>in vitro</i> and <i>in vivo</i> experiments showed that hAT-MSCs possess migratory abilities to target BTICs isolated from medulloblastoma, atypical teratoid/rhabdoid tumors (AT/RT) and glioblastoma. Different types of cyto-chemokines are involved in the crosstalk between hAT-MSCs and BTICs (medulloblastoma and AT/RT: CXCR4/SDF-1, CCR5/RANTES, IL6R/IL-6 and IL8R/IL8; glioblastoma: CXCR4/SDF-1, IL6R/IL-6, IL8R/IL-8 and IGF1R/IGF-1). Our findings demonstrated the migratory ability of hAT-MSCs for BTICs, implying the potential use of MSCs as a delivery vehicle for gene therapy. This study also confirmed the expression of hAT-MSCs cytokine receptors and the BTIC ligands that play roles in their crosstalk.</p></div>", "links"=>[], "tags"=>["crosstalk", "target BTICs", "ccr", "igf", "IL 8R glioblastoma", "mRNA expression patterns", "1r", "cxcr", "tumor tropism capacities", "6r", "vivo bioluminescence imaging analysis", "Gene therapy", "msc", "nsc"], "article_id"=>1450584, "categories"=>["Biological Sciences"], "users"=>["Seung Ah Choi", "Ji Yeoun Lee", "Sung Eun Kwon", "Kyu-Chang Wang", "Ji Hoon Phi", "Jung Won Choi", "Xiong Jin", "Ja Yun Lim", "Hyunggee Kim", "Seung-Ki Kim"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0129292.s001", "https://dx.doi.org/10.1371/journal.pone.0129292.s002", "https://dx.doi.org/10.1371/journal.pone.0129292.s003", "https://dx.doi.org/10.1371/journal.pone.0129292.s004", "https://dx.doi.org/10.1371/journal.pone.0129292.s005"], "stats"=>{"downloads"=>5, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Human_Adipose_Tissue_Derived_Mesenchymal_Stem_Cells_Target_Brain_Tumor_Initiating_Cells_/1450584", "title"=>"Human Adipose Tissue-Derived Mesenchymal Stem Cells Target Brain Tumor-Initiating Cells", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-06-15 04:37:16"}

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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Time
2019-04-06 02:41:26 UTC
Target URL
http://counter-101.soma.plos.org/api/v1.0/stats/doi/10.1371%2Fjournal.pone.0129292
Trace

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