Microenvironmental Interaction Between Hypoxia and Endothelial Cells Controls the Migration Ability of Placenta-Derived Mesenchymal Stem Cells via α4 Integrin and Rho Signaling
ABSTRACT Mesenchymal stem cells (MSCs) are a powerful source for cell therapy in degenerative diseases. The migration ability of MSCs is an important factor that enhances the therapeutic effect of the cells when they are transplanted into target tissues or organs. Hypoxia and the endothelial barrier...
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| Veröffentlicht in: | Journal of cellular biochemistry 2016-05, Vol.117 (5), p.1145-1157 |
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| creator | Choi, Jong Ho Lim, Seung Mook Yoo, Yong In Jung, Jieun Park, Jong-Won Kim, Gi Jin |
| description | ABSTRACT
Mesenchymal stem cells (MSCs) are a powerful source for cell therapy in degenerative diseases. The migration ability of MSCs is an important factor that enhances the therapeutic effect of the cells when they are transplanted into target tissues or organs. Hypoxia and the endothelial barrier, which are representative migration microenvironmental factors, are known to be regulated by the integrin‐mediated pathway in several cancers. However, their regulatory mechanisms in MSCs remain unclear. Here, the objectives of the study were to compare the expression of markers related to integrin‐mediated signaling in placenta‐derived MSCs (PDMSCs) dependent on hypoxia and co‐cultured with human umbilical vein endothelial cells (HUVECs) and to evaluate their correlations between migration ability and microenvironmetal factors including hypoxia and endothelial cells. The migration abilities of PDMSCs exposed to hypoxic conditions were significantly increased compared with normal fibroblasts (WI‐38) and control (P |
| doi_str_mv | 10.1002/jcb.25398 |
| format | Article |
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Mesenchymal stem cells (MSCs) are a powerful source for cell therapy in degenerative diseases. The migration ability of MSCs is an important factor that enhances the therapeutic effect of the cells when they are transplanted into target tissues or organs. Hypoxia and the endothelial barrier, which are representative migration microenvironmental factors, are known to be regulated by the integrin‐mediated pathway in several cancers. However, their regulatory mechanisms in MSCs remain unclear. Here, the objectives of the study were to compare the expression of markers related to integrin‐mediated signaling in placenta‐derived MSCs (PDMSCs) dependent on hypoxia and co‐cultured with human umbilical vein endothelial cells (HUVECs) and to evaluate their correlations between migration ability and microenvironmetal factors including hypoxia and endothelial cells. The migration abilities of PDMSCs exposed to hypoxic conditions were significantly increased compared with normal fibroblasts (WI‐38) and control (P < 0.05). Interestingly, decreased integrin α4 in PDMSCs under hypoxia induce to increase migration abilities of PDMSCs. Also, Rho family‐related markers were significantly increased in PDMSCs under hypoxic conditions compared with normoxia (P < 0.05). Furthermore, the migration ability of PDMSCs was decreased by Rho kinase inhibitor treatment (Y‐27632) and co‐culturing with HUVECs in an ex vivo system. ROCK activity was increased by inhibiting integrin α4 with HUVECs and hypoxia compared with the absence of HUVECs and under normoxia. The findings suggest microenvironment event by hypoxia and the interaction with endothelial cells may be useful as a regulator of MSC migration and provide insight into the migratory mechanism of MSCs in stem cell‐based therapy. J. Cell. Biochem. 117: 1145–1157, 2016. © 2015 Wiley Periodicals, Inc.</description><identifier>ISSN: 0730-2312</identifier><identifier>EISSN: 1097-4644</identifier><identifier>DOI: 10.1002/jcb.25398</identifier><identifier>PMID: 26448639</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Amides - pharmacology ; Blotting, Western ; Cell Hypoxia ; Cell Line ; Cell Movement ; Cells, Cultured ; Cellular Microenvironment ; Coculture Techniques ; Enzyme Inhibitors - pharmacology ; Female ; Fibroblasts - cytology ; Fibroblasts - metabolism ; Gene Expression ; HOMING ; HUMAN UMBILICAL VEIN ENDOTHELIAL CELL (HUVEC) ; Human Umbilical Vein Endothelial Cells - cytology ; Human Umbilical Vein Endothelial Cells - metabolism ; Humans ; HYPOXIA ; Integrin alpha4 - genetics ; Integrin alpha4 - metabolism ; INTEGRIN α4 ; Matrix Metalloproteinase 2 - genetics ; Matrix Metalloproteinase 2 - metabolism ; Mesenchymal Stromal Cells - cytology ; Mesenchymal Stromal Cells - metabolism ; Placenta - cytology ; PLACENTA-DERIVED MESENCHYMAL STEM CELLS ; Pregnancy ; Pyridines - pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; RHO FAMILY ; rho-Associated Kinases - antagonists & inhibitors ; rho-Associated Kinases - genetics ; rho-Associated Kinases - metabolism ; RNA Interference ; Signal Transduction - genetics</subject><ispartof>Journal of cellular biochemistry, 2016-05, Vol.117 (5), p.1145-1157</ispartof><rights>2015 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4148-620789a01f246f08801a2ef679494af4c18826d9f65c25790b7837dc7cb47bbc3</citedby><cites>FETCH-LOGICAL-c4148-620789a01f246f08801a2ef679494af4c18826d9f65c25790b7837dc7cb47bbc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcb.25398$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcb.25398$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27928,27929,45578,45579</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26448639$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Choi, Jong Ho</creatorcontrib><creatorcontrib>Lim, Seung Mook</creatorcontrib><creatorcontrib>Yoo, Yong In</creatorcontrib><creatorcontrib>Jung, Jieun</creatorcontrib><creatorcontrib>Park, Jong-Won</creatorcontrib><creatorcontrib>Kim, Gi Jin</creatorcontrib><title>Microenvironmental Interaction Between Hypoxia and Endothelial Cells Controls the Migration Ability of Placenta-Derived Mesenchymal Stem Cells via α4 Integrin and Rho Signaling</title><title>Journal of cellular biochemistry</title><addtitle>J. Cell. Biochem</addtitle><description>ABSTRACT
Mesenchymal stem cells (MSCs) are a powerful source for cell therapy in degenerative diseases. The migration ability of MSCs is an important factor that enhances the therapeutic effect of the cells when they are transplanted into target tissues or organs. Hypoxia and the endothelial barrier, which are representative migration microenvironmental factors, are known to be regulated by the integrin‐mediated pathway in several cancers. However, their regulatory mechanisms in MSCs remain unclear. Here, the objectives of the study were to compare the expression of markers related to integrin‐mediated signaling in placenta‐derived MSCs (PDMSCs) dependent on hypoxia and co‐cultured with human umbilical vein endothelial cells (HUVECs) and to evaluate their correlations between migration ability and microenvironmetal factors including hypoxia and endothelial cells. The migration abilities of PDMSCs exposed to hypoxic conditions were significantly increased compared with normal fibroblasts (WI‐38) and control (P < 0.05). Interestingly, decreased integrin α4 in PDMSCs under hypoxia induce to increase migration abilities of PDMSCs. Also, Rho family‐related markers were significantly increased in PDMSCs under hypoxic conditions compared with normoxia (P < 0.05). Furthermore, the migration ability of PDMSCs was decreased by Rho kinase inhibitor treatment (Y‐27632) and co‐culturing with HUVECs in an ex vivo system. ROCK activity was increased by inhibiting integrin α4 with HUVECs and hypoxia compared with the absence of HUVECs and under normoxia. The findings suggest microenvironment event by hypoxia and the interaction with endothelial cells may be useful as a regulator of MSC migration and provide insight into the migratory mechanism of MSCs in stem cell‐based therapy. J. Cell. Biochem. 117: 1145–1157, 2016. © 2015 Wiley Periodicals, Inc.</description><subject>Amides - pharmacology</subject><subject>Blotting, Western</subject><subject>Cell Hypoxia</subject><subject>Cell Line</subject><subject>Cell Movement</subject><subject>Cells, Cultured</subject><subject>Cellular Microenvironment</subject><subject>Coculture Techniques</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Female</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - metabolism</subject><subject>Gene Expression</subject><subject>HOMING</subject><subject>HUMAN UMBILICAL VEIN ENDOTHELIAL CELL (HUVEC)</subject><subject>Human Umbilical Vein Endothelial Cells - cytology</subject><subject>Human Umbilical Vein Endothelial Cells - metabolism</subject><subject>Humans</subject><subject>HYPOXIA</subject><subject>Integrin alpha4 - genetics</subject><subject>Integrin alpha4 - metabolism</subject><subject>INTEGRIN α4</subject><subject>Matrix Metalloproteinase 2 - genetics</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Mesenchymal Stromal Cells - metabolism</subject><subject>Placenta - cytology</subject><subject>PLACENTA-DERIVED MESENCHYMAL STEM CELLS</subject><subject>Pregnancy</subject><subject>Pyridines - pharmacology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RHO FAMILY</subject><subject>rho-Associated Kinases - antagonists & inhibitors</subject><subject>rho-Associated Kinases - genetics</subject><subject>rho-Associated Kinases - metabolism</subject><subject>RNA Interference</subject><subject>Signal Transduction - genetics</subject><issn>0730-2312</issn><issn>1097-4644</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc9y0zAQhz0MDA2FAy_A6EgPbiVZseRj65T-oYYOheGokeV1omJLQXLS-rH6IjxT1STtjZM02m-_3dEvST4SfEgwpke3uj6k06wQr5IJwQVPWc7Y62SCeYZTmhG6l7wL4RZjXBQZfZvs0VgXeVZMkofKaO_Aro13tgc7qA5d2AG80oNxFp3AcAdg0fm4dPdGIWUbdGobNyygM5EtoesCKp0dvIuX-IwqM_dq03xcm84MI3Ituu6UfrKnM_BmDQ2qIIDVi7GPkpsB-p1pHWf8e2CbHebe2M3AHwuHbszcqs7Y-fvkTau6AB92537y68vpz_I8vfp-dlEeX6WaESbSnGIuCoVJS1neYiEwURTanBesYKplmghB86Zo86mmU17gmouMN5rrmvG61tl-8nnrXXr3dwVhkL0JOi6pLLhVkIRzLLgQYhrRgy0avzIED61cetMrP0qC5VNCMiYkNwlF9tNOu6p7aF7I50gicLQF7kwH4_9N8rI8eVam2w4TBrh_6VD-j8x5xqfy97czOatENftKqLzOHgEjS6yR</recordid><startdate>201605</startdate><enddate>201605</enddate><creator>Choi, Jong Ho</creator><creator>Lim, Seung Mook</creator><creator>Yoo, Yong In</creator><creator>Jung, Jieun</creator><creator>Park, Jong-Won</creator><creator>Kim, Gi Jin</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</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>7X8</scope></search><sort><creationdate>201605</creationdate><title>Microenvironmental Interaction Between Hypoxia and Endothelial Cells Controls the Migration Ability of Placenta-Derived Mesenchymal Stem Cells via α4 Integrin and Rho Signaling</title><author>Choi, Jong Ho ; Lim, Seung Mook ; Yoo, Yong In ; Jung, Jieun ; Park, Jong-Won ; Kim, Gi Jin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4148-620789a01f246f08801a2ef679494af4c18826d9f65c25790b7837dc7cb47bbc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Amides - pharmacology</topic><topic>Blotting, Western</topic><topic>Cell Hypoxia</topic><topic>Cell Line</topic><topic>Cell Movement</topic><topic>Cells, Cultured</topic><topic>Cellular Microenvironment</topic><topic>Coculture Techniques</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Female</topic><topic>Fibroblasts - cytology</topic><topic>Fibroblasts - metabolism</topic><topic>Gene Expression</topic><topic>HOMING</topic><topic>HUMAN UMBILICAL VEIN ENDOTHELIAL CELL (HUVEC)</topic><topic>Human Umbilical Vein Endothelial Cells - cytology</topic><topic>Human Umbilical Vein Endothelial Cells - metabolism</topic><topic>Humans</topic><topic>HYPOXIA</topic><topic>Integrin alpha4 - genetics</topic><topic>Integrin alpha4 - metabolism</topic><topic>INTEGRIN α4</topic><topic>Matrix Metalloproteinase 2 - genetics</topic><topic>Matrix Metalloproteinase 2 - metabolism</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Mesenchymal Stromal Cells - metabolism</topic><topic>Placenta - cytology</topic><topic>PLACENTA-DERIVED MESENCHYMAL STEM CELLS</topic><topic>Pregnancy</topic><topic>Pyridines - pharmacology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RHO FAMILY</topic><topic>rho-Associated Kinases - antagonists & inhibitors</topic><topic>rho-Associated Kinases - genetics</topic><topic>rho-Associated Kinases - metabolism</topic><topic>RNA Interference</topic><topic>Signal Transduction - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Choi, Jong Ho</creatorcontrib><creatorcontrib>Lim, Seung Mook</creatorcontrib><creatorcontrib>Yoo, Yong In</creatorcontrib><creatorcontrib>Jung, Jieun</creatorcontrib><creatorcontrib>Park, Jong-Won</creatorcontrib><creatorcontrib>Kim, Gi Jin</creatorcontrib><collection>Istex</collection><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><jtitle>Journal of cellular biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Choi, Jong Ho</au><au>Lim, Seung Mook</au><au>Yoo, Yong In</au><au>Jung, Jieun</au><au>Park, Jong-Won</au><au>Kim, Gi Jin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Microenvironmental Interaction Between Hypoxia and Endothelial Cells Controls the Migration Ability of Placenta-Derived Mesenchymal Stem Cells via α4 Integrin and Rho Signaling</atitle><jtitle>Journal of cellular biochemistry</jtitle><addtitle>J. Cell. Biochem</addtitle><date>2016-05</date><risdate>2016</risdate><volume>117</volume><issue>5</issue><spage>1145</spage><epage>1157</epage><pages>1145-1157</pages><issn>0730-2312</issn><eissn>1097-4644</eissn><abstract>ABSTRACT
Mesenchymal stem cells (MSCs) are a powerful source for cell therapy in degenerative diseases. The migration ability of MSCs is an important factor that enhances the therapeutic effect of the cells when they are transplanted into target tissues or organs. Hypoxia and the endothelial barrier, which are representative migration microenvironmental factors, are known to be regulated by the integrin‐mediated pathway in several cancers. However, their regulatory mechanisms in MSCs remain unclear. Here, the objectives of the study were to compare the expression of markers related to integrin‐mediated signaling in placenta‐derived MSCs (PDMSCs) dependent on hypoxia and co‐cultured with human umbilical vein endothelial cells (HUVECs) and to evaluate their correlations between migration ability and microenvironmetal factors including hypoxia and endothelial cells. The migration abilities of PDMSCs exposed to hypoxic conditions were significantly increased compared with normal fibroblasts (WI‐38) and control (P < 0.05). Interestingly, decreased integrin α4 in PDMSCs under hypoxia induce to increase migration abilities of PDMSCs. Also, Rho family‐related markers were significantly increased in PDMSCs under hypoxic conditions compared with normoxia (P < 0.05). Furthermore, the migration ability of PDMSCs was decreased by Rho kinase inhibitor treatment (Y‐27632) and co‐culturing with HUVECs in an ex vivo system. ROCK activity was increased by inhibiting integrin α4 with HUVECs and hypoxia compared with the absence of HUVECs and under normoxia. The findings suggest microenvironment event by hypoxia and the interaction with endothelial cells may be useful as a regulator of MSC migration and provide insight into the migratory mechanism of MSCs in stem cell‐based therapy. J. Cell. Biochem. 117: 1145–1157, 2016. © 2015 Wiley Periodicals, Inc.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>26448639</pmid><doi>10.1002/jcb.25398</doi><tpages>13</tpages></addata></record> |
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| subjects | Amides - pharmacology Blotting, Western Cell Hypoxia Cell Line Cell Movement Cells, Cultured Cellular Microenvironment Coculture Techniques Enzyme Inhibitors - pharmacology Female Fibroblasts - cytology Fibroblasts - metabolism Gene Expression HOMING HUMAN UMBILICAL VEIN ENDOTHELIAL CELL (HUVEC) Human Umbilical Vein Endothelial Cells - cytology Human Umbilical Vein Endothelial Cells - metabolism Humans HYPOXIA Integrin alpha4 - genetics Integrin alpha4 - metabolism INTEGRIN α4 Matrix Metalloproteinase 2 - genetics Matrix Metalloproteinase 2 - metabolism Mesenchymal Stromal Cells - cytology Mesenchymal Stromal Cells - metabolism Placenta - cytology PLACENTA-DERIVED MESENCHYMAL STEM CELLS Pregnancy Pyridines - pharmacology Reverse Transcriptase Polymerase Chain Reaction RHO FAMILY rho-Associated Kinases - antagonists & inhibitors rho-Associated Kinases - genetics rho-Associated Kinases - metabolism RNA Interference Signal Transduction - genetics |
| title | Microenvironmental Interaction Between Hypoxia and Endothelial Cells Controls the Migration Ability of Placenta-Derived Mesenchymal Stem Cells via α4 Integrin and Rho Signaling |
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