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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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 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_910663062</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>866252319</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-eb9240a7b8ac86b43de7c550ef2498e8b638f22faff8a3e7c7f33e38be8af7673</originalsourceid><addsrcrecordid>eNqFkD1PwzAURS0EoqXwA1hQNqbAs53YzogqvqRKMJTZctLnNlUSFzsZ8u9xKWWE6Um-515Zh5BrCncUQN4HAK5oCpSmlBciHU_IlGacp8BzOCVTYLlIJWQwIRchbAForlhxTiaMskIxmU3J8t1jwK7CxNlk3dSuNUno_f6038FmbE0Tn7BNKmyakNRdErPB113s-H7jererq2O3dStsLsmZNU3Aq587Ix9Pj8v5S7p4e36dPyzSisu8T7EsWAZGlspUSpQZX6Gs8hzQsqxQqErBlWXMGmuV4TGTlnPkqkRlrBSSz8jtYXfn3eeAoddtHfa_NB26IeiCghAcBPuXVEKwnHFaRJIeyMq7EDxavfN1a_yoKei9dX2wrqN1vbeux9i5-VkfyhZXv42j5giwAxBi1K3R660bfBfd_LH6BcRnjmg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>866252319</pqid></control><display><type>article</type><title>Presence of glioma stroma mesenchymal stem cells in a murine orthotopic glioma model</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><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.</creator><creatorcontrib>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.</creatorcontrib><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><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 & 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 & 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 & 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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