Presence of glioma stroma mesenchymal stem cells in a murine orthotopic glioma model

Purpose High-grade gliomas are closely related to the mesenchymal phenotype which might be explained by unorthodox differentiation of glioma cancer stem cells (gCSCs). We reasoned that other non-neural stem cells, especially mesenchymal stem cells (MSCs), might play a role in expresssing mesenchymal...

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Veröffentlicht in:Child's nervous system 2011-06, Vol.27 (6), p.911-922
Hauptverfasser: Kim, Sang-Mok, Kang, Seok-Gu, Park, Na-Ri, Mok, Hyun-Su, Huh, Yong-Min, Lee, Su-Jae, Jeun, Sin-Soo, Hong, Yong-Kil, Park, Chun-Kun, Lang, Frederick F.
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container_end_page 922
container_issue 6
container_start_page 911
container_title Child's nervous system
container_volume 27
creator Kim, Sang-Mok
Kang, Seok-Gu
Park, Na-Ri
Mok, Hyun-Su
Huh, Yong-Min
Lee, Su-Jae
Jeun, Sin-Soo
Hong, Yong-Kil
Park, Chun-Kun
Lang, Frederick F.
description Purpose High-grade gliomas are closely related to the mesenchymal phenotype which might be explained by unorthodox differentiation of glioma cancer stem cells (gCSCs). We reasoned that other non-neural stem cells, especially mesenchymal stem cells (MSCs), might play a role in expresssing mesenchymal phenotype of high-grade gliomas. Thus we hypothesized that cells resembling MSCs exist in glioma specimens. Methods We created a mouse (m) orthotopic glioma model using human gCSCs. Single-cell suspensions were isolated from glioma specimens and cultured according to the methods for mMSCs or gliomaspheres. These cells were analyzed by fluorescence-activated cell sorting (FACS) for surface markers associated with mMSCs or gCSCs. Glioma stroma (GS)-MSCs were exposed to mesenchymal differentiation conditions. To decide the location of GS-MSCs, sections of orthotopic glioma models were analyzed by immunofluorescent labeling. Results GS-MSCs were isolated which were morphologically similar to mMSCs. FACS analysis showed that the GS-MSCs had similar surface markers to mMSCs (stem cell antigen-1 [Sca-1] + , CD9 + , CD45 − , CD11b − , CD31 − , and nerve/glial antigen 2 [NG2] − ). GS-MSCs were capable of mesenchymal differentiation. Immunofluorescent labeling indicated that GS-MSCs are located around blood vessels, are distinct from endothelial cells, and have features that partially overlap with vascular pericytes. Conclusions Our results indicate that cells similar to mMSCs exist in glioma specimens. The GS-MSCs might be located around vessels, which suggests that GS-MSCs may provide the mesenchymal elements of the vascular niche. GS-MSCs may represent non-neural stem cells that act as an important source of mesenchymal elements, particularly during the growth of gliomas.
doi_str_mv 10.1007/s00381-011-1396-y
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We reasoned that other non-neural stem cells, especially mesenchymal stem cells (MSCs), might play a role in expresssing mesenchymal phenotype of high-grade gliomas. Thus we hypothesized that cells resembling MSCs exist in glioma specimens. Methods We created a mouse (m) orthotopic glioma model using human gCSCs. Single-cell suspensions were isolated from glioma specimens and cultured according to the methods for mMSCs or gliomaspheres. These cells were analyzed by fluorescence-activated cell sorting (FACS) for surface markers associated with mMSCs or gCSCs. Glioma stroma (GS)-MSCs were exposed to mesenchymal differentiation conditions. To decide the location of GS-MSCs, sections of orthotopic glioma models were analyzed by immunofluorescent labeling. Results GS-MSCs were isolated which were morphologically similar to mMSCs. FACS analysis showed that the GS-MSCs had similar surface markers to mMSCs (stem cell antigen-1 [Sca-1] + , CD9 + , CD45 − , CD11b − , CD31 − , and nerve/glial antigen 2 [NG2] − ). GS-MSCs were capable of mesenchymal differentiation. Immunofluorescent labeling indicated that GS-MSCs are located around blood vessels, are distinct from endothelial cells, and have features that partially overlap with vascular pericytes. Conclusions Our results indicate that cells similar to mMSCs exist in glioma specimens. The GS-MSCs might be located around vessels, which suggests that GS-MSCs may provide the mesenchymal elements of the vascular niche. GS-MSCs may represent non-neural stem cells that act as an important source of mesenchymal elements, particularly during the growth of gliomas.</description><identifier>ISSN: 0256-7040</identifier><identifier>EISSN: 1433-0350</identifier><identifier>DOI: 10.1007/s00381-011-1396-y</identifier><identifier>PMID: 21298274</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Animals ; Brain Neoplasms - etiology ; Brain Neoplasms - pathology ; Cell Differentiation - physiology ; Disease Models, Animal ; Glioma - etiology ; Glioma - pathology ; Humans ; Male ; Medicine ; Medicine &amp; Public Health ; Mesenchymal Stromal Cells - pathology ; Mice ; Mice, Nude ; Neurosciences ; Neurosurgery ; Original Paper ; Stromal Cells - pathology ; Stromal Cells - physiology ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays - methods</subject><ispartof>Child's nervous system, 2011-06, Vol.27 (6), p.911-922</ispartof><rights>Springer-Verlag 2011</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-eb9240a7b8ac86b43de7c550ef2498e8b638f22faff8a3e7c7f33e38be8af7673</citedby><cites>FETCH-LOGICAL-c375t-eb9240a7b8ac86b43de7c550ef2498e8b638f22faff8a3e7c7f33e38be8af7673</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00381-011-1396-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00381-011-1396-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21298274$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Sang-Mok</creatorcontrib><creatorcontrib>Kang, Seok-Gu</creatorcontrib><creatorcontrib>Park, Na-Ri</creatorcontrib><creatorcontrib>Mok, Hyun-Su</creatorcontrib><creatorcontrib>Huh, Yong-Min</creatorcontrib><creatorcontrib>Lee, Su-Jae</creatorcontrib><creatorcontrib>Jeun, Sin-Soo</creatorcontrib><creatorcontrib>Hong, Yong-Kil</creatorcontrib><creatorcontrib>Park, Chun-Kun</creatorcontrib><creatorcontrib>Lang, Frederick F.</creatorcontrib><title>Presence of glioma stroma mesenchymal stem cells in a murine orthotopic glioma model</title><title>Child's nervous system</title><addtitle>Childs Nerv Syst</addtitle><addtitle>Childs Nerv Syst</addtitle><description>Purpose High-grade gliomas are closely related to the mesenchymal phenotype which might be explained by unorthodox differentiation of glioma cancer stem cells (gCSCs). We reasoned that other non-neural stem cells, especially mesenchymal stem cells (MSCs), might play a role in expresssing mesenchymal phenotype of high-grade gliomas. Thus we hypothesized that cells resembling MSCs exist in glioma specimens. Methods We created a mouse (m) orthotopic glioma model using human gCSCs. Single-cell suspensions were isolated from glioma specimens and cultured according to the methods for mMSCs or gliomaspheres. These cells were analyzed by fluorescence-activated cell sorting (FACS) for surface markers associated with mMSCs or gCSCs. Glioma stroma (GS)-MSCs were exposed to mesenchymal differentiation conditions. To decide the location of GS-MSCs, sections of orthotopic glioma models were analyzed by immunofluorescent labeling. Results GS-MSCs were isolated which were morphologically similar to mMSCs. FACS analysis showed that the GS-MSCs had similar surface markers to mMSCs (stem cell antigen-1 [Sca-1] + , CD9 + , CD45 − , CD11b − , CD31 − , and nerve/glial antigen 2 [NG2] − ). GS-MSCs were capable of mesenchymal differentiation. Immunofluorescent labeling indicated that GS-MSCs are located around blood vessels, are distinct from endothelial cells, and have features that partially overlap with vascular pericytes. Conclusions Our results indicate that cells similar to mMSCs exist in glioma specimens. The GS-MSCs might be located around vessels, which suggests that GS-MSCs may provide the mesenchymal elements of the vascular niche. GS-MSCs may represent non-neural stem cells that act as an important source of mesenchymal elements, particularly during the growth of gliomas.</description><subject>Animals</subject><subject>Brain Neoplasms - etiology</subject><subject>Brain Neoplasms - pathology</subject><subject>Cell Differentiation - physiology</subject><subject>Disease Models, Animal</subject><subject>Glioma - etiology</subject><subject>Glioma - pathology</subject><subject>Humans</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Mesenchymal Stromal Cells - pathology</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Neurosciences</subject><subject>Neurosurgery</subject><subject>Original Paper</subject><subject>Stromal Cells - pathology</subject><subject>Stromal Cells - physiology</subject><subject>Tumor Cells, Cultured</subject><subject>Xenograft Model Antitumor Assays - methods</subject><issn>0256-7040</issn><issn>1433-0350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkD1PwzAURS0EoqXwA1hQNqbAs53YzogqvqRKMJTZctLnNlUSFzsZ8u9xKWWE6Um-515Zh5BrCncUQN4HAK5oCpSmlBciHU_IlGacp8BzOCVTYLlIJWQwIRchbAForlhxTiaMskIxmU3J8t1jwK7CxNlk3dSuNUno_f6038FmbE0Tn7BNKmyakNRdErPB113s-H7jererq2O3dStsLsmZNU3Aq587Ix9Pj8v5S7p4e36dPyzSisu8T7EsWAZGlspUSpQZX6Gs8hzQsqxQqErBlWXMGmuV4TGTlnPkqkRlrBSSz8jtYXfn3eeAoddtHfa_NB26IeiCghAcBPuXVEKwnHFaRJIeyMq7EDxavfN1a_yoKei9dX2wrqN1vbeux9i5-VkfyhZXv42j5giwAxBi1K3R660bfBfd_LH6BcRnjmg</recordid><startdate>20110601</startdate><enddate>20110601</enddate><creator>Kim, Sang-Mok</creator><creator>Kang, Seok-Gu</creator><creator>Park, Na-Ri</creator><creator>Mok, Hyun-Su</creator><creator>Huh, Yong-Min</creator><creator>Lee, Su-Jae</creator><creator>Jeun, Sin-Soo</creator><creator>Hong, Yong-Kil</creator><creator>Park, Chun-Kun</creator><creator>Lang, Frederick F.</creator><general>Springer-Verlag</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TK</scope></search><sort><creationdate>20110601</creationdate><title>Presence of glioma stroma mesenchymal stem cells in a murine orthotopic glioma model</title><author>Kim, Sang-Mok ; Kang, Seok-Gu ; Park, Na-Ri ; Mok, Hyun-Su ; Huh, Yong-Min ; Lee, Su-Jae ; Jeun, Sin-Soo ; Hong, Yong-Kil ; Park, Chun-Kun ; Lang, Frederick F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-eb9240a7b8ac86b43de7c550ef2498e8b638f22faff8a3e7c7f33e38be8af7673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Brain Neoplasms - etiology</topic><topic>Brain Neoplasms - pathology</topic><topic>Cell Differentiation - physiology</topic><topic>Disease Models, Animal</topic><topic>Glioma - etiology</topic><topic>Glioma - pathology</topic><topic>Humans</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine &amp; Public Health</topic><topic>Mesenchymal Stromal Cells - pathology</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Neurosciences</topic><topic>Neurosurgery</topic><topic>Original Paper</topic><topic>Stromal Cells - pathology</topic><topic>Stromal Cells - physiology</topic><topic>Tumor Cells, Cultured</topic><topic>Xenograft Model Antitumor Assays - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Sang-Mok</creatorcontrib><creatorcontrib>Kang, Seok-Gu</creatorcontrib><creatorcontrib>Park, Na-Ri</creatorcontrib><creatorcontrib>Mok, Hyun-Su</creatorcontrib><creatorcontrib>Huh, Yong-Min</creatorcontrib><creatorcontrib>Lee, Su-Jae</creatorcontrib><creatorcontrib>Jeun, Sin-Soo</creatorcontrib><creatorcontrib>Hong, Yong-Kil</creatorcontrib><creatorcontrib>Park, Chun-Kun</creatorcontrib><creatorcontrib>Lang, Frederick F.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><jtitle>Child's nervous system</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Sang-Mok</au><au>Kang, Seok-Gu</au><au>Park, Na-Ri</au><au>Mok, Hyun-Su</au><au>Huh, Yong-Min</au><au>Lee, Su-Jae</au><au>Jeun, Sin-Soo</au><au>Hong, Yong-Kil</au><au>Park, Chun-Kun</au><au>Lang, Frederick F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Presence of glioma stroma mesenchymal stem cells in a murine orthotopic glioma model</atitle><jtitle>Child's nervous system</jtitle><stitle>Childs Nerv Syst</stitle><addtitle>Childs Nerv Syst</addtitle><date>2011-06-01</date><risdate>2011</risdate><volume>27</volume><issue>6</issue><spage>911</spage><epage>922</epage><pages>911-922</pages><issn>0256-7040</issn><eissn>1433-0350</eissn><abstract>Purpose High-grade gliomas are closely related to the mesenchymal phenotype which might be explained by unorthodox differentiation of glioma cancer stem cells (gCSCs). We reasoned that other non-neural stem cells, especially mesenchymal stem cells (MSCs), might play a role in expresssing mesenchymal phenotype of high-grade gliomas. Thus we hypothesized that cells resembling MSCs exist in glioma specimens. Methods We created a mouse (m) orthotopic glioma model using human gCSCs. Single-cell suspensions were isolated from glioma specimens and cultured according to the methods for mMSCs or gliomaspheres. These cells were analyzed by fluorescence-activated cell sorting (FACS) for surface markers associated with mMSCs or gCSCs. Glioma stroma (GS)-MSCs were exposed to mesenchymal differentiation conditions. To decide the location of GS-MSCs, sections of orthotopic glioma models were analyzed by immunofluorescent labeling. Results GS-MSCs were isolated which were morphologically similar to mMSCs. FACS analysis showed that the GS-MSCs had similar surface markers to mMSCs (stem cell antigen-1 [Sca-1] + , CD9 + , CD45 − , CD11b − , CD31 − , and nerve/glial antigen 2 [NG2] − ). GS-MSCs were capable of mesenchymal differentiation. Immunofluorescent labeling indicated that GS-MSCs are located around blood vessels, are distinct from endothelial cells, and have features that partially overlap with vascular pericytes. Conclusions Our results indicate that cells similar to mMSCs exist in glioma specimens. The GS-MSCs might be located around vessels, which suggests that GS-MSCs may provide the mesenchymal elements of the vascular niche. GS-MSCs may represent non-neural stem cells that act as an important source of mesenchymal elements, particularly during the growth of gliomas.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>21298274</pmid><doi>10.1007/s00381-011-1396-y</doi><tpages>12</tpages></addata></record>
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source MEDLINE; Springer Nature - Complete Springer Journals
subjects Animals
Brain Neoplasms - etiology
Brain Neoplasms - pathology
Cell Differentiation - physiology
Disease Models, Animal
Glioma - etiology
Glioma - pathology
Humans
Male
Medicine
Medicine & Public Health
Mesenchymal Stromal Cells - pathology
Mice
Mice, Nude
Neurosciences
Neurosurgery
Original Paper
Stromal Cells - pathology
Stromal Cells - physiology
Tumor Cells, Cultured
Xenograft Model Antitumor Assays - methods
title Presence of glioma stroma mesenchymal stem cells in a murine orthotopic glioma model
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