Development of Versatile Human In Vitro Vascularized Adipose Tissue Model with Serum‐Free Angiogenesis and Natural Adipogenesis Induction
Many adipose tissue‐related diseases, such as obesity and type 2 diabetes, are worldwide epidemics. For studying these diseases, relevant human cell models are needed. In this study, we developed a vascularized adipose tissue model where human adipose stromal cells and human umbilical cord vein endo...
Gespeichert in:
| Veröffentlicht in: | Basic & clinical pharmacology & toxicology 2018-09, Vol.123 (S5), p.62-71 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 71 |
|---|---|
| container_issue | S5 |
| container_start_page | 62 |
| container_title | Basic & clinical pharmacology & toxicology |
| container_volume | 123 |
| creator | Huttala, Outi Palmroth, Maaria Hemminki, Pauliina Toimela, Tarja Heinonen, Tuula Ylikomi, Timo Sarkanen, Jertta‐Riina |
| description | Many adipose tissue‐related diseases, such as obesity and type 2 diabetes, are worldwide epidemics. For studying these diseases, relevant human cell models are needed. In this study, we developed a vascularized adipose tissue model where human adipose stromal cells and human umbilical cord vein endothelial cells were cocultured with natural adipogenic and defined serum‐free angiogenic media for 14 days. Several different protocols were compared to each other. The protocols varied in cell numbers and plating sequences. Lipid accumulation was studied with AdipoRed reagent, relative cell number with WST‐1 reagent, gene expression of glut4, leptin, aP2, adiponectin, PPARγ and PPARγ2 with RT‐qPCR. Secretion of adiponectin, leptin and aP2 was analysed with ELISA. The immunostained vascular network was imaged with Cell‐IQ and area quantified using ImageJ. In this study, both angiogenesis and adipogenesis were successfully induced. Protocols produced strong lipid accumulation, good vascular network formation and induced adipocyte‐specific protein secretion and expression of studied adipocyte genes. Results showed that cell numbers and cell plating sequences are important factors when aiming at in vitro standardized tissue model. Presence of mature vasculature appeared leads to faster the maturation of adipocytes judged by the lipid accumulation and gene expression results. The developed vascularized adipose tissue model is simple to use, easily modifiable to suit various applications and as such, a promising new tool for adipose tissue research when, for example, studying the effect of different cell types on adipose tissue function or for mechanistic studies. |
| doi_str_mv | 10.1111/bcpt.12987 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2113073257</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2113073257</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3937-900a1c0a6a36c02eee486247bd82d0c17fb51cb7c77610a313835203090d551e3</originalsourceid><addsrcrecordid>eNp9kMlOwzAQhi0EYilceABkiRtSi5ekbo6lbJXYJEqvkWNPwSixgx2D4MSdC8_IkxAIcGQuM9J884_0IbRNyYC2tV-ouhlQlo3EElqnImF9MUr48t_M0zW0EcI9IUwklKyiNZYlCU9Sto7eDuERSldXYBvsFngOPsjGlIBPYyUtnlo8N413eC6DiqX05gU0HmtTuwB4ZkKIgM-dhhI_meYOX4OP1cfr-7EHwGN7a9wtWAgmYGk1vpBN9LLs7n8XU6ujaoyzm2hlIcsAWz-9h26Oj2aT0_7Z5cl0Mj7rK55x0c8IkVQROZR8qAgDgGQ0ZIko9IhpoqhYFClVhVBCDCmRnPLWACOcZESnKQXeQ7tdbu3dQ4TQ5Pcuetu-zBmlnAjOUtFSex2lvAvBwyKvvamkf84pyb-851_e82_vLbzzExmLCvQf-iu6BWgHPLVun_-Jyg8mV7Mu9BMqjo9r</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2113073257</pqid></control><display><type>article</type><title>Development of Versatile Human In Vitro Vascularized Adipose Tissue Model with Serum‐Free Angiogenesis and Natural Adipogenesis Induction</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><source>Alma/SFX Local Collection</source><creator>Huttala, Outi ; Palmroth, Maaria ; Hemminki, Pauliina ; Toimela, Tarja ; Heinonen, Tuula ; Ylikomi, Timo ; Sarkanen, Jertta‐Riina</creator><creatorcontrib>Huttala, Outi ; Palmroth, Maaria ; Hemminki, Pauliina ; Toimela, Tarja ; Heinonen, Tuula ; Ylikomi, Timo ; Sarkanen, Jertta‐Riina</creatorcontrib><description>Many adipose tissue‐related diseases, such as obesity and type 2 diabetes, are worldwide epidemics. For studying these diseases, relevant human cell models are needed. In this study, we developed a vascularized adipose tissue model where human adipose stromal cells and human umbilical cord vein endothelial cells were cocultured with natural adipogenic and defined serum‐free angiogenic media for 14 days. Several different protocols were compared to each other. The protocols varied in cell numbers and plating sequences. Lipid accumulation was studied with AdipoRed reagent, relative cell number with WST‐1 reagent, gene expression of glut4, leptin, aP2, adiponectin, PPARγ and PPARγ2 with RT‐qPCR. Secretion of adiponectin, leptin and aP2 was analysed with ELISA. The immunostained vascular network was imaged with Cell‐IQ and area quantified using ImageJ. In this study, both angiogenesis and adipogenesis were successfully induced. Protocols produced strong lipid accumulation, good vascular network formation and induced adipocyte‐specific protein secretion and expression of studied adipocyte genes. Results showed that cell numbers and cell plating sequences are important factors when aiming at in vitro standardized tissue model. Presence of mature vasculature appeared leads to faster the maturation of adipocytes judged by the lipid accumulation and gene expression results. The developed vascularized adipose tissue model is simple to use, easily modifiable to suit various applications and as such, a promising new tool for adipose tissue research when, for example, studying the effect of different cell types on adipose tissue function or for mechanistic studies.</description><identifier>ISSN: 1742-7835</identifier><identifier>EISSN: 1742-7843</identifier><identifier>DOI: 10.1111/bcpt.12987</identifier><identifier>PMID: 29443452</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Accumulation ; Adipocytes ; Adipogenesis ; Adiponectin ; Adiponectin - genetics ; Adiponectin - metabolism ; Adipose tissue ; Adipose Tissue - blood supply ; Adipose Tissue - cytology ; Adipose Tissue - metabolism ; Angiogenesis ; Cell culture ; Cell Culture Techniques - methods ; Cell number ; Coculture Techniques - methods ; Culture Media, Serum-Free ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - etiology ; Diabetes Mellitus, Type 2 - metabolism ; Endothelial cells ; Enzyme-linked immunosorbent assay ; Epidemics ; Fatty Acid-Binding Proteins - genetics ; Fatty Acid-Binding Proteins - metabolism ; Gene expression ; Gene sequencing ; Glucose Transporter Type 4 - genetics ; Human Umbilical Vein Endothelial Cells ; Humans ; Leptin ; Leptin - genetics ; Leptin - metabolism ; Lipid Metabolism - physiology ; Lipids ; Maturation ; Medical imaging ; Neovascularization, Physiologic ; Network formation ; Obesity - etiology ; Obesity - metabolism ; PPAR gamma - genetics ; Proteins ; Protocol (computers) ; Reagents ; RNA, Messenger - metabolism ; Stromal cells ; Umbilical cord</subject><ispartof>Basic & clinical pharmacology & toxicology, 2018-09, Vol.123 (S5), p.62-71</ispartof><rights>2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society)</rights><rights>2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).</rights><rights>Copyright © 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3937-900a1c0a6a36c02eee486247bd82d0c17fb51cb7c77610a313835203090d551e3</citedby><cites>FETCH-LOGICAL-c3937-900a1c0a6a36c02eee486247bd82d0c17fb51cb7c77610a313835203090d551e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fbcpt.12987$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fbcpt.12987$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29443452$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huttala, Outi</creatorcontrib><creatorcontrib>Palmroth, Maaria</creatorcontrib><creatorcontrib>Hemminki, Pauliina</creatorcontrib><creatorcontrib>Toimela, Tarja</creatorcontrib><creatorcontrib>Heinonen, Tuula</creatorcontrib><creatorcontrib>Ylikomi, Timo</creatorcontrib><creatorcontrib>Sarkanen, Jertta‐Riina</creatorcontrib><title>Development of Versatile Human In Vitro Vascularized Adipose Tissue Model with Serum‐Free Angiogenesis and Natural Adipogenesis Induction</title><title>Basic & clinical pharmacology & toxicology</title><addtitle>Basic Clin Pharmacol Toxicol</addtitle><description>Many adipose tissue‐related diseases, such as obesity and type 2 diabetes, are worldwide epidemics. For studying these diseases, relevant human cell models are needed. In this study, we developed a vascularized adipose tissue model where human adipose stromal cells and human umbilical cord vein endothelial cells were cocultured with natural adipogenic and defined serum‐free angiogenic media for 14 days. Several different protocols were compared to each other. The protocols varied in cell numbers and plating sequences. Lipid accumulation was studied with AdipoRed reagent, relative cell number with WST‐1 reagent, gene expression of glut4, leptin, aP2, adiponectin, PPARγ and PPARγ2 with RT‐qPCR. Secretion of adiponectin, leptin and aP2 was analysed with ELISA. The immunostained vascular network was imaged with Cell‐IQ and area quantified using ImageJ. In this study, both angiogenesis and adipogenesis were successfully induced. Protocols produced strong lipid accumulation, good vascular network formation and induced adipocyte‐specific protein secretion and expression of studied adipocyte genes. Results showed that cell numbers and cell plating sequences are important factors when aiming at in vitro standardized tissue model. Presence of mature vasculature appeared leads to faster the maturation of adipocytes judged by the lipid accumulation and gene expression results. The developed vascularized adipose tissue model is simple to use, easily modifiable to suit various applications and as such, a promising new tool for adipose tissue research when, for example, studying the effect of different cell types on adipose tissue function or for mechanistic studies.</description><subject>Accumulation</subject><subject>Adipocytes</subject><subject>Adipogenesis</subject><subject>Adiponectin</subject><subject>Adiponectin - genetics</subject><subject>Adiponectin - metabolism</subject><subject>Adipose tissue</subject><subject>Adipose Tissue - blood supply</subject><subject>Adipose Tissue - cytology</subject><subject>Adipose Tissue - metabolism</subject><subject>Angiogenesis</subject><subject>Cell culture</subject><subject>Cell Culture Techniques - methods</subject><subject>Cell number</subject><subject>Coculture Techniques - methods</subject><subject>Culture Media, Serum-Free</subject><subject>Diabetes mellitus</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2 - etiology</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Endothelial cells</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Epidemics</subject><subject>Fatty Acid-Binding Proteins - genetics</subject><subject>Fatty Acid-Binding Proteins - metabolism</subject><subject>Gene expression</subject><subject>Gene sequencing</subject><subject>Glucose Transporter Type 4 - genetics</subject><subject>Human Umbilical Vein Endothelial Cells</subject><subject>Humans</subject><subject>Leptin</subject><subject>Leptin - genetics</subject><subject>Leptin - metabolism</subject><subject>Lipid Metabolism - physiology</subject><subject>Lipids</subject><subject>Maturation</subject><subject>Medical imaging</subject><subject>Neovascularization, Physiologic</subject><subject>Network formation</subject><subject>Obesity - etiology</subject><subject>Obesity - metabolism</subject><subject>PPAR gamma - genetics</subject><subject>Proteins</subject><subject>Protocol (computers)</subject><subject>Reagents</subject><subject>RNA, Messenger - metabolism</subject><subject>Stromal cells</subject><subject>Umbilical cord</subject><issn>1742-7835</issn><issn>1742-7843</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMlOwzAQhi0EYilceABkiRtSi5ekbo6lbJXYJEqvkWNPwSixgx2D4MSdC8_IkxAIcGQuM9J884_0IbRNyYC2tV-ouhlQlo3EElqnImF9MUr48t_M0zW0EcI9IUwklKyiNZYlCU9Sto7eDuERSldXYBvsFngOPsjGlIBPYyUtnlo8N413eC6DiqX05gU0HmtTuwB4ZkKIgM-dhhI_meYOX4OP1cfr-7EHwGN7a9wtWAgmYGk1vpBN9LLs7n8XU6ujaoyzm2hlIcsAWz-9h26Oj2aT0_7Z5cl0Mj7rK55x0c8IkVQROZR8qAgDgGQ0ZIko9IhpoqhYFClVhVBCDCmRnPLWACOcZESnKQXeQ7tdbu3dQ4TQ5Pcuetu-zBmlnAjOUtFSex2lvAvBwyKvvamkf84pyb-851_e82_vLbzzExmLCvQf-iu6BWgHPLVun_-Jyg8mV7Mu9BMqjo9r</recordid><startdate>201809</startdate><enddate>201809</enddate><creator>Huttala, Outi</creator><creator>Palmroth, Maaria</creator><creator>Hemminki, Pauliina</creator><creator>Toimela, Tarja</creator><creator>Heinonen, Tuula</creator><creator>Ylikomi, Timo</creator><creator>Sarkanen, Jertta‐Riina</creator><general>Wiley Subscription Services, Inc</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>7QP</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>201809</creationdate><title>Development of Versatile Human In Vitro Vascularized Adipose Tissue Model with Serum‐Free Angiogenesis and Natural Adipogenesis Induction</title><author>Huttala, Outi ; Palmroth, Maaria ; Hemminki, Pauliina ; Toimela, Tarja ; Heinonen, Tuula ; Ylikomi, Timo ; Sarkanen, Jertta‐Riina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3937-900a1c0a6a36c02eee486247bd82d0c17fb51cb7c77610a313835203090d551e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Accumulation</topic><topic>Adipocytes</topic><topic>Adipogenesis</topic><topic>Adiponectin</topic><topic>Adiponectin - genetics</topic><topic>Adiponectin - metabolism</topic><topic>Adipose tissue</topic><topic>Adipose Tissue - blood supply</topic><topic>Adipose Tissue - cytology</topic><topic>Adipose Tissue - metabolism</topic><topic>Angiogenesis</topic><topic>Cell culture</topic><topic>Cell Culture Techniques - methods</topic><topic>Cell number</topic><topic>Coculture Techniques - methods</topic><topic>Culture Media, Serum-Free</topic><topic>Diabetes mellitus</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Type 2 - etiology</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Endothelial cells</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Epidemics</topic><topic>Fatty Acid-Binding Proteins - genetics</topic><topic>Fatty Acid-Binding Proteins - metabolism</topic><topic>Gene expression</topic><topic>Gene sequencing</topic><topic>Glucose Transporter Type 4 - genetics</topic><topic>Human Umbilical Vein Endothelial Cells</topic><topic>Humans</topic><topic>Leptin</topic><topic>Leptin - genetics</topic><topic>Leptin - metabolism</topic><topic>Lipid Metabolism - physiology</topic><topic>Lipids</topic><topic>Maturation</topic><topic>Medical imaging</topic><topic>Neovascularization, Physiologic</topic><topic>Network formation</topic><topic>Obesity - etiology</topic><topic>Obesity - metabolism</topic><topic>PPAR gamma - genetics</topic><topic>Proteins</topic><topic>Protocol (computers)</topic><topic>Reagents</topic><topic>RNA, Messenger - metabolism</topic><topic>Stromal cells</topic><topic>Umbilical cord</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huttala, Outi</creatorcontrib><creatorcontrib>Palmroth, Maaria</creatorcontrib><creatorcontrib>Hemminki, Pauliina</creatorcontrib><creatorcontrib>Toimela, Tarja</creatorcontrib><creatorcontrib>Heinonen, Tuula</creatorcontrib><creatorcontrib>Ylikomi, Timo</creatorcontrib><creatorcontrib>Sarkanen, Jertta‐Riina</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Basic & clinical pharmacology & toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huttala, Outi</au><au>Palmroth, Maaria</au><au>Hemminki, Pauliina</au><au>Toimela, Tarja</au><au>Heinonen, Tuula</au><au>Ylikomi, Timo</au><au>Sarkanen, Jertta‐Riina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development of Versatile Human In Vitro Vascularized Adipose Tissue Model with Serum‐Free Angiogenesis and Natural Adipogenesis Induction</atitle><jtitle>Basic & clinical pharmacology & toxicology</jtitle><addtitle>Basic Clin Pharmacol Toxicol</addtitle><date>2018-09</date><risdate>2018</risdate><volume>123</volume><issue>S5</issue><spage>62</spage><epage>71</epage><pages>62-71</pages><issn>1742-7835</issn><eissn>1742-7843</eissn><abstract>Many adipose tissue‐related diseases, such as obesity and type 2 diabetes, are worldwide epidemics. For studying these diseases, relevant human cell models are needed. In this study, we developed a vascularized adipose tissue model where human adipose stromal cells and human umbilical cord vein endothelial cells were cocultured with natural adipogenic and defined serum‐free angiogenic media for 14 days. Several different protocols were compared to each other. The protocols varied in cell numbers and plating sequences. Lipid accumulation was studied with AdipoRed reagent, relative cell number with WST‐1 reagent, gene expression of glut4, leptin, aP2, adiponectin, PPARγ and PPARγ2 with RT‐qPCR. Secretion of adiponectin, leptin and aP2 was analysed with ELISA. The immunostained vascular network was imaged with Cell‐IQ and area quantified using ImageJ. In this study, both angiogenesis and adipogenesis were successfully induced. Protocols produced strong lipid accumulation, good vascular network formation and induced adipocyte‐specific protein secretion and expression of studied adipocyte genes. Results showed that cell numbers and cell plating sequences are important factors when aiming at in vitro standardized tissue model. Presence of mature vasculature appeared leads to faster the maturation of adipocytes judged by the lipid accumulation and gene expression results. The developed vascularized adipose tissue model is simple to use, easily modifiable to suit various applications and as such, a promising new tool for adipose tissue research when, for example, studying the effect of different cell types on adipose tissue function or for mechanistic studies.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>29443452</pmid><doi>10.1111/bcpt.12987</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1742-7835 |
| ispartof | Basic & clinical pharmacology & toxicology, 2018-09, Vol.123 (S5), p.62-71 |
| issn | 1742-7835 1742-7843 |
| language | eng |
| recordid | cdi_proquest_journals_2113073257 |
| source | MEDLINE; Access via Wiley Online Library; Alma/SFX Local Collection |
| subjects | Accumulation Adipocytes Adipogenesis Adiponectin Adiponectin - genetics Adiponectin - metabolism Adipose tissue Adipose Tissue - blood supply Adipose Tissue - cytology Adipose Tissue - metabolism Angiogenesis Cell culture Cell Culture Techniques - methods Cell number Coculture Techniques - methods Culture Media, Serum-Free Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - etiology Diabetes Mellitus, Type 2 - metabolism Endothelial cells Enzyme-linked immunosorbent assay Epidemics Fatty Acid-Binding Proteins - genetics Fatty Acid-Binding Proteins - metabolism Gene expression Gene sequencing Glucose Transporter Type 4 - genetics Human Umbilical Vein Endothelial Cells Humans Leptin Leptin - genetics Leptin - metabolism Lipid Metabolism - physiology Lipids Maturation Medical imaging Neovascularization, Physiologic Network formation Obesity - etiology Obesity - metabolism PPAR gamma - genetics Proteins Protocol (computers) Reagents RNA, Messenger - metabolism Stromal cells Umbilical cord |
| title | Development of Versatile Human In Vitro Vascularized Adipose Tissue Model with Serum‐Free Angiogenesis and Natural Adipogenesis Induction |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T18%3A38%3A42IST&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=Development%20of%20Versatile%20Human%20In%20Vitro%20Vascularized%20Adipose%20Tissue%20Model%20with%20Serum%E2%80%90Free%20Angiogenesis%20and%20Natural%20Adipogenesis%20Induction&rft.jtitle=Basic%20&%20clinical%20pharmacology%20&%20toxicology&rft.au=Huttala,%20Outi&rft.date=2018-09&rft.volume=123&rft.issue=S5&rft.spage=62&rft.epage=71&rft.pages=62-71&rft.issn=1742-7835&rft.eissn=1742-7843&rft_id=info:doi/10.1111/bcpt.12987&rft_dat=%3Cproquest_cross%3E2113073257%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=2113073257&rft_id=info:pmid/29443452&rfr_iscdi=true |