Mesenchymal stem cells in rheumatoid synovium: enumeration and functional assessment in relation to synovial inflammation level
Objective:Achieving joint regeneration in rheumatoid arthritis (RA) represents a future challenge. Autologous synovial mesenchymal stem cells (MSCs) could be therapeutically exploited. However, the inflammatory milieu in the RA synovium could adversely affect endogenous MSC function. To test this hy...
Gespeichert in:
| Veröffentlicht in: | Annals of the rheumatic diseases 2010-02, Vol.69 (2), p.450-457 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 457 |
|---|---|
| container_issue | 2 |
| container_start_page | 450 |
| container_title | Annals of the rheumatic diseases |
| container_volume | 69 |
| creator | Jones, E Churchman, S M English, A Buch, M H Horner, E A Burgoyne, C H Reece, R Kinsey, S Emery, P McGonagle, D Ponchel, F |
| description | Objective:Achieving joint regeneration in rheumatoid arthritis (RA) represents a future challenge. Autologous synovial mesenchymal stem cells (MSCs) could be therapeutically exploited. However, the inflammatory milieu in the RA synovium could adversely affect endogenous MSC function. To test this hypothesis, the frequency and multipotency of RA synovial MSCs was evaluated in relation to existing synovial inflammation.Methods:Synovial inflammation was measured using the arthroscopic visual analogue score (VAS) and further validated using immunohistochemistry and flow cytometry. Highly proliferative clonogenic in vivo MSCs were enumerated following fluorescence-activated cell sorting and expansion for 20 population doublings. MSC multipotency was quantified following standard in vitro culture expansion and trilineage differentiation assays. Real-time PCR, flow cytometry and ELISA were used to evaluate pro- and anti-chondrogenic molecules in standard polyclonal synovial MSCs.Results:The arthroscopic VAS significantly correlated with synovial macrophage infiltration. In RA, synovial MSC chondrogenesis was inhibited in direct relation to VAS (r = −0.777, p |
| doi_str_mv | 10.1136/ard.2008.106435 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_734260013</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>734260013</sourcerecordid><originalsourceid>FETCH-LOGICAL-b529t-c02df5ff5cfd6bc24d0313223538a7141ae22d90c9b4462eff659df558f0f7663</originalsourceid><addsrcrecordid>eNqN0duL1DAUBvAgiju7-uybFEQWlM7m0iatbzp4g_ECXl5Dmp6wHZt0N6ddnCf_dTO27IAg-BQO-X0hh4-QR4yuGRPywsR2zSmt1ozKQpR3yIoVsso5lfQuWVFKRV7UUp2QU8RdGmnFqvvkhNWikJzVK_LrAyAEe7n3ps9wBJ9Z6HvMupDFS5i8GYeuzXAfhptu8i8yCJOHaMZuCJkJbeamYA9DShtEQPQQxj9p6Gc1Dks8kS643ng_X_RwA_0Dcs-ZHuHhcp6Rb29ef928y7ef3r7fvNzmTcnrMbeUt650rrSulY3lRUsFE5yLUlRGsYIZ4Lytqa2bIm0GzsmyTomyctQpKcUZOZ_fvYrD9QQ4at_hYVUTYJhQK1FwSSkTST75S-6GKaYFUTOlVFUqReukLmZl44AYwemr2HkT95pRfahGp2r0oRo9V5MSj5d3p8ZDe_RLFwk8XYBBa3oXTbAd3jrOeVVzVSSXz65Lff28vTfxh5ZKqFJ__L7RfCO-fGb8ld4m_2z2jd_9xy-fH_Fx8X_o3-pSwjk</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1777857709</pqid></control><display><type>article</type><title>Mesenchymal stem cells in rheumatoid synovium: enumeration and functional assessment in relation to synovial inflammation level</title><source>MEDLINE</source><source>BMJ Journals - NESLi2</source><creator>Jones, E ; Churchman, S M ; English, A ; Buch, M H ; Horner, E A ; Burgoyne, C H ; Reece, R ; Kinsey, S ; Emery, P ; McGonagle, D ; Ponchel, F</creator><creatorcontrib>Jones, E ; Churchman, S M ; English, A ; Buch, M H ; Horner, E A ; Burgoyne, C H ; Reece, R ; Kinsey, S ; Emery, P ; McGonagle, D ; Ponchel, F</creatorcontrib><description>Objective:Achieving joint regeneration in rheumatoid arthritis (RA) represents a future challenge. Autologous synovial mesenchymal stem cells (MSCs) could be therapeutically exploited. However, the inflammatory milieu in the RA synovium could adversely affect endogenous MSC function. To test this hypothesis, the frequency and multipotency of RA synovial MSCs was evaluated in relation to existing synovial inflammation.Methods:Synovial inflammation was measured using the arthroscopic visual analogue score (VAS) and further validated using immunohistochemistry and flow cytometry. Highly proliferative clonogenic in vivo MSCs were enumerated following fluorescence-activated cell sorting and expansion for 20 population doublings. MSC multipotency was quantified following standard in vitro culture expansion and trilineage differentiation assays. Real-time PCR, flow cytometry and ELISA were used to evaluate pro- and anti-chondrogenic molecules in standard polyclonal synovial MSCs.Results:The arthroscopic VAS significantly correlated with synovial macrophage infiltration. In RA, synovial MSC chondrogenesis was inhibited in direct relation to VAS (r = −0.777, p<0.05) and reduced compared with control osteoarthritis (OA)-MSCs (p<0.05). In vivo, MSCs resided in the synovial fibroblastic/stromal fraction (CD45−CD31−) and were reduced in frequency in relation to VAS (r = −0.695, p<0.05). In RA-MSCs, CD44 levels correlated negatively with inflammation and positively with chondrogenesis (r = −0.830 and r = 0.865, respectively). Cytokine production and Sox9 expression was similar in RA-MSCs and OA-MSCs.Conclusions:There is a negative relationship between synovial MSC chondrogenic and clonogenic capacities and the magnitude of synovitis in RA. Effective suppression of joint inflammation is therefore necessary for the development of autologous MSC treatments aimed at cartilage regeneration in RA.</description><identifier>ISSN: 0003-4967</identifier><identifier>EISSN: 1468-2060</identifier><identifier>DOI: 10.1136/ard.2008.106435</identifier><identifier>PMID: 19346219</identifier><identifier>CODEN: ARDIAO</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd and European League Against Rheumatism</publisher><subject>Adult ; Aged ; Arthritis, Rheumatoid - pathology ; Arthroscopy ; Basic and translational research ; Biological and medical sciences ; Biopsy ; Cartilage diseases ; CD44 antigen ; CD45 antigen ; Cell Count ; Cell culture ; Cell Differentiation ; Cells, Cultured ; Chondrogenesis ; Chondrogenesis - physiology ; Cloning ; Cytokines - biosynthesis ; Diseases of the osteoarticular system ; Enumeration ; Enzyme-linked immunosorbent assay ; Female ; Fibroblasts ; Flow cytometry ; Gene expression ; Humans ; Hypotheses ; Immunohistochemistry ; Inflammation ; Inflammatory joint diseases ; Joint surgery ; Macrophages ; Male ; Medical sciences ; Mesenchymal stem cells ; Mesenchymal Stem Cells - metabolism ; Mesenchymal Stem Cells - pathology ; Mesenchymal Stem Cells - physiology ; Middle Aged ; Osteoarthritis ; Osteoarthritis - pathology ; Patients ; Phenotype ; Rheumatoid arthritis ; Rheumatoid synovitis ; Rheumatoid synovium ; Senescence ; Severity of Illness Index ; Sox9 protein ; Stem cells ; Synovitis ; Synovitis - pathology</subject><ispartof>Annals of the rheumatic diseases, 2010-02, Vol.69 (2), p.450-457</ispartof><rights>BMJ Publishing Group Ltd and European League Against Rheumatism. All rights reserved.</rights><rights>2015 INIST-CNRS</rights><rights>BMJ Publishing Group Ltd and European League Against Rheumatism. All rights reserved.2010</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b529t-c02df5ff5cfd6bc24d0313223538a7141ae22d90c9b4462eff659df558f0f7663</citedby><cites>FETCH-LOGICAL-b529t-c02df5ff5cfd6bc24d0313223538a7141ae22d90c9b4462eff659df558f0f7663</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://ard.bmj.com/content/69/2/450.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttp://ard.bmj.com/content/69/2/450.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>114,115,314,776,780,3183,23550,27901,27902,55321,77343,77374,77402,77428</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22289274$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19346219$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jones, E</creatorcontrib><creatorcontrib>Churchman, S M</creatorcontrib><creatorcontrib>English, A</creatorcontrib><creatorcontrib>Buch, M H</creatorcontrib><creatorcontrib>Horner, E A</creatorcontrib><creatorcontrib>Burgoyne, C H</creatorcontrib><creatorcontrib>Reece, R</creatorcontrib><creatorcontrib>Kinsey, S</creatorcontrib><creatorcontrib>Emery, P</creatorcontrib><creatorcontrib>McGonagle, D</creatorcontrib><creatorcontrib>Ponchel, F</creatorcontrib><title>Mesenchymal stem cells in rheumatoid synovium: enumeration and functional assessment in relation to synovial inflammation level</title><title>Annals of the rheumatic diseases</title><addtitle>Ann Rheum Dis</addtitle><addtitle>Ann Rheum Dis</addtitle><description>Objective:Achieving joint regeneration in rheumatoid arthritis (RA) represents a future challenge. Autologous synovial mesenchymal stem cells (MSCs) could be therapeutically exploited. However, the inflammatory milieu in the RA synovium could adversely affect endogenous MSC function. To test this hypothesis, the frequency and multipotency of RA synovial MSCs was evaluated in relation to existing synovial inflammation.Methods:Synovial inflammation was measured using the arthroscopic visual analogue score (VAS) and further validated using immunohistochemistry and flow cytometry. Highly proliferative clonogenic in vivo MSCs were enumerated following fluorescence-activated cell sorting and expansion for 20 population doublings. MSC multipotency was quantified following standard in vitro culture expansion and trilineage differentiation assays. Real-time PCR, flow cytometry and ELISA were used to evaluate pro- and anti-chondrogenic molecules in standard polyclonal synovial MSCs.Results:The arthroscopic VAS significantly correlated with synovial macrophage infiltration. In RA, synovial MSC chondrogenesis was inhibited in direct relation to VAS (r = −0.777, p<0.05) and reduced compared with control osteoarthritis (OA)-MSCs (p<0.05). In vivo, MSCs resided in the synovial fibroblastic/stromal fraction (CD45−CD31−) and were reduced in frequency in relation to VAS (r = −0.695, p<0.05). In RA-MSCs, CD44 levels correlated negatively with inflammation and positively with chondrogenesis (r = −0.830 and r = 0.865, respectively). Cytokine production and Sox9 expression was similar in RA-MSCs and OA-MSCs.Conclusions:There is a negative relationship between synovial MSC chondrogenic and clonogenic capacities and the magnitude of synovitis in RA. Effective suppression of joint inflammation is therefore necessary for the development of autologous MSC treatments aimed at cartilage regeneration in RA.</description><subject>Adult</subject><subject>Aged</subject><subject>Arthritis, Rheumatoid - pathology</subject><subject>Arthroscopy</subject><subject>Basic and translational research</subject><subject>Biological and medical sciences</subject><subject>Biopsy</subject><subject>Cartilage diseases</subject><subject>CD44 antigen</subject><subject>CD45 antigen</subject><subject>Cell Count</subject><subject>Cell culture</subject><subject>Cell Differentiation</subject><subject>Cells, Cultured</subject><subject>Chondrogenesis</subject><subject>Chondrogenesis - physiology</subject><subject>Cloning</subject><subject>Cytokines - biosynthesis</subject><subject>Diseases of the osteoarticular system</subject><subject>Enumeration</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Flow cytometry</subject><subject>Gene expression</subject><subject>Humans</subject><subject>Hypotheses</subject><subject>Immunohistochemistry</subject><subject>Inflammation</subject><subject>Inflammatory joint diseases</subject><subject>Joint surgery</subject><subject>Macrophages</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stem Cells - metabolism</subject><subject>Mesenchymal Stem Cells - pathology</subject><subject>Mesenchymal Stem Cells - physiology</subject><subject>Middle Aged</subject><subject>Osteoarthritis</subject><subject>Osteoarthritis - pathology</subject><subject>Patients</subject><subject>Phenotype</subject><subject>Rheumatoid arthritis</subject><subject>Rheumatoid synovitis</subject><subject>Rheumatoid synovium</subject><subject>Senescence</subject><subject>Severity of Illness Index</subject><subject>Sox9 protein</subject><subject>Stem cells</subject><subject>Synovitis</subject><subject>Synovitis - pathology</subject><issn>0003-4967</issn><issn>1468-2060</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqN0duL1DAUBvAgiju7-uybFEQWlM7m0iatbzp4g_ECXl5Dmp6wHZt0N6ddnCf_dTO27IAg-BQO-X0hh4-QR4yuGRPywsR2zSmt1ozKQpR3yIoVsso5lfQuWVFKRV7UUp2QU8RdGmnFqvvkhNWikJzVK_LrAyAEe7n3ps9wBJ9Z6HvMupDFS5i8GYeuzXAfhptu8i8yCJOHaMZuCJkJbeamYA9DShtEQPQQxj9p6Gc1Dks8kS643ng_X_RwA_0Dcs-ZHuHhcp6Rb29ef928y7ef3r7fvNzmTcnrMbeUt650rrSulY3lRUsFE5yLUlRGsYIZ4Lytqa2bIm0GzsmyTomyctQpKcUZOZ_fvYrD9QQ4at_hYVUTYJhQK1FwSSkTST75S-6GKaYFUTOlVFUqReukLmZl44AYwemr2HkT95pRfahGp2r0oRo9V5MSj5d3p8ZDe_RLFwk8XYBBa3oXTbAd3jrOeVVzVSSXz65Lff28vTfxh5ZKqFJ__L7RfCO-fGb8ld4m_2z2jd_9xy-fH_Fx8X_o3-pSwjk</recordid><startdate>20100201</startdate><enddate>20100201</enddate><creator>Jones, E</creator><creator>Churchman, S M</creator><creator>English, A</creator><creator>Buch, M H</creator><creator>Horner, E A</creator><creator>Burgoyne, C H</creator><creator>Reece, R</creator><creator>Kinsey, S</creator><creator>Emery, P</creator><creator>McGonagle, D</creator><creator>Ponchel, F</creator><general>BMJ Publishing Group Ltd and European League Against Rheumatism</general><general>BMJ Publishing Group</general><general>Elsevier Limited</general><scope>BSCLL</scope><scope>IQODW</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20100201</creationdate><title>Mesenchymal stem cells in rheumatoid synovium: enumeration and functional assessment in relation to synovial inflammation level</title><author>Jones, E ; Churchman, S M ; English, A ; Buch, M H ; Horner, E A ; Burgoyne, C H ; Reece, R ; Kinsey, S ; Emery, P ; McGonagle, D ; Ponchel, F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b529t-c02df5ff5cfd6bc24d0313223538a7141ae22d90c9b4462eff659df558f0f7663</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Arthritis, Rheumatoid - pathology</topic><topic>Arthroscopy</topic><topic>Basic and translational research</topic><topic>Biological and medical sciences</topic><topic>Biopsy</topic><topic>Cartilage diseases</topic><topic>CD44 antigen</topic><topic>CD45 antigen</topic><topic>Cell Count</topic><topic>Cell culture</topic><topic>Cell Differentiation</topic><topic>Cells, Cultured</topic><topic>Chondrogenesis</topic><topic>Chondrogenesis - physiology</topic><topic>Cloning</topic><topic>Cytokines - biosynthesis</topic><topic>Diseases of the osteoarticular system</topic><topic>Enumeration</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Female</topic><topic>Fibroblasts</topic><topic>Flow cytometry</topic><topic>Gene expression</topic><topic>Humans</topic><topic>Hypotheses</topic><topic>Immunohistochemistry</topic><topic>Inflammation</topic><topic>Inflammatory joint diseases</topic><topic>Joint surgery</topic><topic>Macrophages</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mesenchymal stem cells</topic><topic>Mesenchymal Stem Cells - metabolism</topic><topic>Mesenchymal Stem Cells - pathology</topic><topic>Mesenchymal Stem Cells - physiology</topic><topic>Middle Aged</topic><topic>Osteoarthritis</topic><topic>Osteoarthritis - pathology</topic><topic>Patients</topic><topic>Phenotype</topic><topic>Rheumatoid arthritis</topic><topic>Rheumatoid synovitis</topic><topic>Rheumatoid synovium</topic><topic>Senescence</topic><topic>Severity of Illness Index</topic><topic>Sox9 protein</topic><topic>Stem cells</topic><topic>Synovitis</topic><topic>Synovitis - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jones, E</creatorcontrib><creatorcontrib>Churchman, S M</creatorcontrib><creatorcontrib>English, A</creatorcontrib><creatorcontrib>Buch, M H</creatorcontrib><creatorcontrib>Horner, E A</creatorcontrib><creatorcontrib>Burgoyne, C H</creatorcontrib><creatorcontrib>Reece, R</creatorcontrib><creatorcontrib>Kinsey, S</creatorcontrib><creatorcontrib>Emery, P</creatorcontrib><creatorcontrib>McGonagle, D</creatorcontrib><creatorcontrib>Ponchel, F</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of the rheumatic diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jones, E</au><au>Churchman, S M</au><au>English, A</au><au>Buch, M H</au><au>Horner, E A</au><au>Burgoyne, C H</au><au>Reece, R</au><au>Kinsey, S</au><au>Emery, P</au><au>McGonagle, D</au><au>Ponchel, F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mesenchymal stem cells in rheumatoid synovium: enumeration and functional assessment in relation to synovial inflammation level</atitle><jtitle>Annals of the rheumatic diseases</jtitle><stitle>Ann Rheum Dis</stitle><addtitle>Ann Rheum Dis</addtitle><date>2010-02-01</date><risdate>2010</risdate><volume>69</volume><issue>2</issue><spage>450</spage><epage>457</epage><pages>450-457</pages><issn>0003-4967</issn><eissn>1468-2060</eissn><coden>ARDIAO</coden><abstract>Objective:Achieving joint regeneration in rheumatoid arthritis (RA) represents a future challenge. Autologous synovial mesenchymal stem cells (MSCs) could be therapeutically exploited. However, the inflammatory milieu in the RA synovium could adversely affect endogenous MSC function. To test this hypothesis, the frequency and multipotency of RA synovial MSCs was evaluated in relation to existing synovial inflammation.Methods:Synovial inflammation was measured using the arthroscopic visual analogue score (VAS) and further validated using immunohistochemistry and flow cytometry. Highly proliferative clonogenic in vivo MSCs were enumerated following fluorescence-activated cell sorting and expansion for 20 population doublings. MSC multipotency was quantified following standard in vitro culture expansion and trilineage differentiation assays. Real-time PCR, flow cytometry and ELISA were used to evaluate pro- and anti-chondrogenic molecules in standard polyclonal synovial MSCs.Results:The arthroscopic VAS significantly correlated with synovial macrophage infiltration. In RA, synovial MSC chondrogenesis was inhibited in direct relation to VAS (r = −0.777, p<0.05) and reduced compared with control osteoarthritis (OA)-MSCs (p<0.05). In vivo, MSCs resided in the synovial fibroblastic/stromal fraction (CD45−CD31−) and were reduced in frequency in relation to VAS (r = −0.695, p<0.05). In RA-MSCs, CD44 levels correlated negatively with inflammation and positively with chondrogenesis (r = −0.830 and r = 0.865, respectively). Cytokine production and Sox9 expression was similar in RA-MSCs and OA-MSCs.Conclusions:There is a negative relationship between synovial MSC chondrogenic and clonogenic capacities and the magnitude of synovitis in RA. Effective suppression of joint inflammation is therefore necessary for the development of autologous MSC treatments aimed at cartilage regeneration in RA.</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd and European League Against Rheumatism</pub><pmid>19346219</pmid><doi>10.1136/ard.2008.106435</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0003-4967 |
| ispartof | Annals of the rheumatic diseases, 2010-02, Vol.69 (2), p.450-457 |
| issn | 0003-4967 1468-2060 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_734260013 |
| source | MEDLINE; BMJ Journals - NESLi2 |
| subjects | Adult Aged Arthritis, Rheumatoid - pathology Arthroscopy Basic and translational research Biological and medical sciences Biopsy Cartilage diseases CD44 antigen CD45 antigen Cell Count Cell culture Cell Differentiation Cells, Cultured Chondrogenesis Chondrogenesis - physiology Cloning Cytokines - biosynthesis Diseases of the osteoarticular system Enumeration Enzyme-linked immunosorbent assay Female Fibroblasts Flow cytometry Gene expression Humans Hypotheses Immunohistochemistry Inflammation Inflammatory joint diseases Joint surgery Macrophages Male Medical sciences Mesenchymal stem cells Mesenchymal Stem Cells - metabolism Mesenchymal Stem Cells - pathology Mesenchymal Stem Cells - physiology Middle Aged Osteoarthritis Osteoarthritis - pathology Patients Phenotype Rheumatoid arthritis Rheumatoid synovitis Rheumatoid synovium Senescence Severity of Illness Index Sox9 protein Stem cells Synovitis Synovitis - pathology |
| title | Mesenchymal stem cells in rheumatoid synovium: enumeration and functional assessment in relation to synovial inflammation level |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T20%3A28%3A46IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mesenchymal%20stem%20cells%20in%20rheumatoid%20synovium:%20enumeration%20and%20functional%20assessment%20in%20relation%20to%20synovial%20inflammation%20level&rft.jtitle=Annals%20of%20the%20rheumatic%20diseases&rft.au=Jones,%20E&rft.date=2010-02-01&rft.volume=69&rft.issue=2&rft.spage=450&rft.epage=457&rft.pages=450-457&rft.issn=0003-4967&rft.eissn=1468-2060&rft.coden=ARDIAO&rft_id=info:doi/10.1136/ard.2008.106435&rft_dat=%3Cproquest_cross%3E734260013%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1777857709&rft_id=info:pmid/19346219&rfr_iscdi=true |