An Autologous Bone Marrow Mesenchymal Stem Cell–Derived Extracellular Matrix Scaffold Applied with Bone Marrow Stimulation for Cartilage Repair

Purpose: It is well known that implanting a bioactive scaffold into a cartilage defect site can enhance cartilage repair after bone marrow stimulation (BMS). However, most of the current scaffolds are derived from xenogenous tissue and/or artificial polymers. The implantation of these scaffolds adds...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Tissue engineering. Part A 2014-09, Vol.20 (17-18), p.2455-2462
Hauptverfasser: Tang, Cheng, Jin, Chengzhe, Du, Xiaotao, Yan, Chao, Min, Byoung-Hyun, Xu, Yan, Wang, Liming
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 2462
container_issue 17-18
container_start_page 2455
container_title Tissue engineering. Part A
container_volume 20
creator Tang, Cheng
Jin, Chengzhe
Du, Xiaotao
Yan, Chao
Min, Byoung-Hyun
Xu, Yan
Wang, Liming
description Purpose: It is well known that implanting a bioactive scaffold into a cartilage defect site can enhance cartilage repair after bone marrow stimulation (BMS). However, most of the current scaffolds are derived from xenogenous tissue and/or artificial polymers. The implantation of these scaffolds adds risks of pathogen transmission, undesirable inflammation, and other immunological reactions, as well as ethical issues in clinical practice. The current study was undertaken to evaluate the effectiveness of implanting autologous bone marrow mesenchymal stem cell–derived extracellular matrix (aBMSC-dECM) scaffolds after BMS for cartilage repair. Methods: Full osteochondral defects were performed on the trochlear groove of both knees in 24 rabbits. One group underwent BMS only in the right knee (the BMS group), and the other group was treated by implantation of the aBMSC-dECM scaffold after BMS in the left knee (the aBMSC-dECM scaffold group). Results: Better repair of cartilage defects was observed in the aBMSC-dECM scaffold group than in the BMS group according to gross observation, histological assessments, immunohistochemistry, and chemical assay. The glycosaminoglycan and DNA content, the distribution of proteoglycan, and the distribution and arrangement of type II and I collagen fibers in the repaired tissue in the aBMSC-dECM scaffold group at 12 weeks after surgery were similar to that surrounding normal hyaline cartilage. Conclusions: Implanting aBMSC-dECM scaffolds can enhance the therapeutic effect of BMS on articular cartilage repair, and this combination treatment is a potential method for successful articular cartilage repair.
doi_str_mv 10.1089/ten.tea.2013.0464
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4161140</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3428916621</sourcerecordid><originalsourceid>FETCH-LOGICAL-c490t-5fe214065d0fa6d666a593c97e3525a9d7387fbb1e7c7149681fb91fbc7ff4693</originalsourceid><addsrcrecordid>eNqNUctu1DAUjRCIlsIHsEGWWM9gx44db5CGoZRKrZAYkNhZTnI948qxg-P0seMXqv5hv6QeTRnRHYsrX12fc-7jFMVbgucE1_JDAj9PoOclJnSOGWfPikMiqZhRWv16vs8ZOShejeMFxhxzIV4WByXjnLNSHha3C48WUwourMM0ok_BAzrXMYYrdA4j-HZz02uHVgl6tATn7v_cfYZoL6FDx9cp6jbXJqdjJqVor9Gq1cYE16HFMDibUVc2bZ7IrpLtMyPZ4JEJES11TNbpNaDvMGgbXxcvjHYjvHl8j4qfX45_LL_Ozr6dnC4XZ7OWSZxmlYGSMMyrDhvNu7yPriRtpQBalZWWnaC1ME1DQLSCMMlrYhqZoxXGMC7pUfFxpztMTQ9dCz6v49QQba_jjQraqqc_3m7UOlwqRjjJnbPA-0eBGH5PMCZ1Eabo88yKVJxQUjNRZxTZodoYxjGC2XcgWG1dVNnFHFptXVRbFzPn3b-j7Rl_bcsAsQNsy9r7fOkGYvoP6QeMTbFK</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1561318478</pqid></control><display><type>article</type><title>An Autologous Bone Marrow Mesenchymal Stem Cell–Derived Extracellular Matrix Scaffold Applied with Bone Marrow Stimulation for Cartilage Repair</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Tang, Cheng ; Jin, Chengzhe ; Du, Xiaotao ; Yan, Chao ; Min, Byoung-Hyun ; Xu, Yan ; Wang, Liming</creator><creatorcontrib>Tang, Cheng ; Jin, Chengzhe ; Du, Xiaotao ; Yan, Chao ; Min, Byoung-Hyun ; Xu, Yan ; Wang, Liming</creatorcontrib><description>Purpose: It is well known that implanting a bioactive scaffold into a cartilage defect site can enhance cartilage repair after bone marrow stimulation (BMS). However, most of the current scaffolds are derived from xenogenous tissue and/or artificial polymers. The implantation of these scaffolds adds risks of pathogen transmission, undesirable inflammation, and other immunological reactions, as well as ethical issues in clinical practice. The current study was undertaken to evaluate the effectiveness of implanting autologous bone marrow mesenchymal stem cell–derived extracellular matrix (aBMSC-dECM) scaffolds after BMS for cartilage repair. Methods: Full osteochondral defects were performed on the trochlear groove of both knees in 24 rabbits. One group underwent BMS only in the right knee (the BMS group), and the other group was treated by implantation of the aBMSC-dECM scaffold after BMS in the left knee (the aBMSC-dECM scaffold group). Results: Better repair of cartilage defects was observed in the aBMSC-dECM scaffold group than in the BMS group according to gross observation, histological assessments, immunohistochemistry, and chemical assay. The glycosaminoglycan and DNA content, the distribution of proteoglycan, and the distribution and arrangement of type II and I collagen fibers in the repaired tissue in the aBMSC-dECM scaffold group at 12 weeks after surgery were similar to that surrounding normal hyaline cartilage. Conclusions: Implanting aBMSC-dECM scaffolds can enhance the therapeutic effect of BMS on articular cartilage repair, and this combination treatment is a potential method for successful articular cartilage repair.</description><identifier>ISSN: 1937-3341</identifier><identifier>EISSN: 1937-335X</identifier><identifier>DOI: 10.1089/ten.tea.2013.0464</identifier><identifier>PMID: 24666429</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Animals ; Autografts ; Bone Marrow - metabolism ; Cartilage ; Cartilage, Articular - growth &amp; development ; Cartilage, Articular - injuries ; Cartilage, Articular - pathology ; Cell Differentiation ; Cells, Cultured ; Cellular biology ; Chondrogenesis - physiology ; Equipment Design ; Extracellular Matrix - transplantation ; Mesenchymal Stem Cell Transplantation - instrumentation ; Mesenchymal Stem Cell Transplantation - methods ; Mesenchymal Stromal Cells - metabolism ; Original ; Original Articles ; Rabbits ; Stem cells ; Tissue engineering ; Tissue Scaffolds</subject><ispartof>Tissue engineering. Part A, 2014-09, Vol.20 (17-18), p.2455-2462</ispartof><rights>2014, Mary Ann Liebert, Inc.</rights><rights>(©) Copyright 2014, Mary Ann Liebert, Inc.</rights><rights>Copyright 2014, Mary Ann Liebert, Inc. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c490t-5fe214065d0fa6d666a593c97e3525a9d7387fbb1e7c7149681fb91fbc7ff4693</citedby><cites>FETCH-LOGICAL-c490t-5fe214065d0fa6d666a593c97e3525a9d7387fbb1e7c7149681fb91fbc7ff4693</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24666429$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tang, Cheng</creatorcontrib><creatorcontrib>Jin, Chengzhe</creatorcontrib><creatorcontrib>Du, Xiaotao</creatorcontrib><creatorcontrib>Yan, Chao</creatorcontrib><creatorcontrib>Min, Byoung-Hyun</creatorcontrib><creatorcontrib>Xu, Yan</creatorcontrib><creatorcontrib>Wang, Liming</creatorcontrib><title>An Autologous Bone Marrow Mesenchymal Stem Cell–Derived Extracellular Matrix Scaffold Applied with Bone Marrow Stimulation for Cartilage Repair</title><title>Tissue engineering. Part A</title><addtitle>Tissue Eng Part A</addtitle><description>Purpose: It is well known that implanting a bioactive scaffold into a cartilage defect site can enhance cartilage repair after bone marrow stimulation (BMS). However, most of the current scaffolds are derived from xenogenous tissue and/or artificial polymers. The implantation of these scaffolds adds risks of pathogen transmission, undesirable inflammation, and other immunological reactions, as well as ethical issues in clinical practice. The current study was undertaken to evaluate the effectiveness of implanting autologous bone marrow mesenchymal stem cell–derived extracellular matrix (aBMSC-dECM) scaffolds after BMS for cartilage repair. Methods: Full osteochondral defects were performed on the trochlear groove of both knees in 24 rabbits. One group underwent BMS only in the right knee (the BMS group), and the other group was treated by implantation of the aBMSC-dECM scaffold after BMS in the left knee (the aBMSC-dECM scaffold group). Results: Better repair of cartilage defects was observed in the aBMSC-dECM scaffold group than in the BMS group according to gross observation, histological assessments, immunohistochemistry, and chemical assay. The glycosaminoglycan and DNA content, the distribution of proteoglycan, and the distribution and arrangement of type II and I collagen fibers in the repaired tissue in the aBMSC-dECM scaffold group at 12 weeks after surgery were similar to that surrounding normal hyaline cartilage. Conclusions: Implanting aBMSC-dECM scaffolds can enhance the therapeutic effect of BMS on articular cartilage repair, and this combination treatment is a potential method for successful articular cartilage repair.</description><subject>Animals</subject><subject>Autografts</subject><subject>Bone Marrow - metabolism</subject><subject>Cartilage</subject><subject>Cartilage, Articular - growth &amp; development</subject><subject>Cartilage, Articular - injuries</subject><subject>Cartilage, Articular - pathology</subject><subject>Cell Differentiation</subject><subject>Cells, Cultured</subject><subject>Cellular biology</subject><subject>Chondrogenesis - physiology</subject><subject>Equipment Design</subject><subject>Extracellular Matrix - transplantation</subject><subject>Mesenchymal Stem Cell Transplantation - instrumentation</subject><subject>Mesenchymal Stem Cell Transplantation - methods</subject><subject>Mesenchymal Stromal Cells - metabolism</subject><subject>Original</subject><subject>Original Articles</subject><subject>Rabbits</subject><subject>Stem cells</subject><subject>Tissue engineering</subject><subject>Tissue Scaffolds</subject><issn>1937-3341</issn><issn>1937-335X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNUctu1DAUjRCIlsIHsEGWWM9gx44db5CGoZRKrZAYkNhZTnI948qxg-P0seMXqv5hv6QeTRnRHYsrX12fc-7jFMVbgucE1_JDAj9PoOclJnSOGWfPikMiqZhRWv16vs8ZOShejeMFxhxzIV4WByXjnLNSHha3C48WUwourMM0ok_BAzrXMYYrdA4j-HZz02uHVgl6tATn7v_cfYZoL6FDx9cp6jbXJqdjJqVor9Gq1cYE16HFMDibUVc2bZ7IrpLtMyPZ4JEJES11TNbpNaDvMGgbXxcvjHYjvHl8j4qfX45_LL_Ozr6dnC4XZ7OWSZxmlYGSMMyrDhvNu7yPriRtpQBalZWWnaC1ME1DQLSCMMlrYhqZoxXGMC7pUfFxpztMTQ9dCz6v49QQba_jjQraqqc_3m7UOlwqRjjJnbPA-0eBGH5PMCZ1Eabo88yKVJxQUjNRZxTZodoYxjGC2XcgWG1dVNnFHFptXVRbFzPn3b-j7Rl_bcsAsQNsy9r7fOkGYvoP6QeMTbFK</recordid><startdate>20140901</startdate><enddate>20140901</enddate><creator>Tang, Cheng</creator><creator>Jin, Chengzhe</creator><creator>Du, Xiaotao</creator><creator>Yan, Chao</creator><creator>Min, Byoung-Hyun</creator><creator>Xu, Yan</creator><creator>Wang, Liming</creator><general>Mary Ann Liebert, 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>3V.</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</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>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</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>5PM</scope></search><sort><creationdate>20140901</creationdate><title>An Autologous Bone Marrow Mesenchymal Stem Cell–Derived Extracellular Matrix Scaffold Applied with Bone Marrow Stimulation for Cartilage Repair</title><author>Tang, Cheng ; Jin, Chengzhe ; Du, Xiaotao ; Yan, Chao ; Min, Byoung-Hyun ; Xu, Yan ; Wang, Liming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c490t-5fe214065d0fa6d666a593c97e3525a9d7387fbb1e7c7149681fb91fbc7ff4693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Autografts</topic><topic>Bone Marrow - metabolism</topic><topic>Cartilage</topic><topic>Cartilage, Articular - growth &amp; development</topic><topic>Cartilage, Articular - injuries</topic><topic>Cartilage, Articular - pathology</topic><topic>Cell Differentiation</topic><topic>Cells, Cultured</topic><topic>Cellular biology</topic><topic>Chondrogenesis - physiology</topic><topic>Equipment Design</topic><topic>Extracellular Matrix - transplantation</topic><topic>Mesenchymal Stem Cell Transplantation - instrumentation</topic><topic>Mesenchymal Stem Cell Transplantation - methods</topic><topic>Mesenchymal Stromal Cells - metabolism</topic><topic>Original</topic><topic>Original Articles</topic><topic>Rabbits</topic><topic>Stem cells</topic><topic>Tissue engineering</topic><topic>Tissue Scaffolds</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tang, Cheng</creatorcontrib><creatorcontrib>Jin, Chengzhe</creatorcontrib><creatorcontrib>Du, Xiaotao</creatorcontrib><creatorcontrib>Yan, Chao</creatorcontrib><creatorcontrib>Min, Byoung-Hyun</creatorcontrib><creatorcontrib>Xu, Yan</creatorcontrib><creatorcontrib>Wang, Liming</creatorcontrib><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>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</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>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>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; 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>PubMed Central (Full Participant titles)</collection><jtitle>Tissue engineering. Part A</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tang, Cheng</au><au>Jin, Chengzhe</au><au>Du, Xiaotao</au><au>Yan, Chao</au><au>Min, Byoung-Hyun</au><au>Xu, Yan</au><au>Wang, Liming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An Autologous Bone Marrow Mesenchymal Stem Cell–Derived Extracellular Matrix Scaffold Applied with Bone Marrow Stimulation for Cartilage Repair</atitle><jtitle>Tissue engineering. Part A</jtitle><addtitle>Tissue Eng Part A</addtitle><date>2014-09-01</date><risdate>2014</risdate><volume>20</volume><issue>17-18</issue><spage>2455</spage><epage>2462</epage><pages>2455-2462</pages><issn>1937-3341</issn><eissn>1937-335X</eissn><abstract>Purpose: It is well known that implanting a bioactive scaffold into a cartilage defect site can enhance cartilage repair after bone marrow stimulation (BMS). However, most of the current scaffolds are derived from xenogenous tissue and/or artificial polymers. The implantation of these scaffolds adds risks of pathogen transmission, undesirable inflammation, and other immunological reactions, as well as ethical issues in clinical practice. The current study was undertaken to evaluate the effectiveness of implanting autologous bone marrow mesenchymal stem cell–derived extracellular matrix (aBMSC-dECM) scaffolds after BMS for cartilage repair. Methods: Full osteochondral defects were performed on the trochlear groove of both knees in 24 rabbits. One group underwent BMS only in the right knee (the BMS group), and the other group was treated by implantation of the aBMSC-dECM scaffold after BMS in the left knee (the aBMSC-dECM scaffold group). Results: Better repair of cartilage defects was observed in the aBMSC-dECM scaffold group than in the BMS group according to gross observation, histological assessments, immunohistochemistry, and chemical assay. The glycosaminoglycan and DNA content, the distribution of proteoglycan, and the distribution and arrangement of type II and I collagen fibers in the repaired tissue in the aBMSC-dECM scaffold group at 12 weeks after surgery were similar to that surrounding normal hyaline cartilage. Conclusions: Implanting aBMSC-dECM scaffolds can enhance the therapeutic effect of BMS on articular cartilage repair, and this combination treatment is a potential method for successful articular cartilage repair.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>24666429</pmid><doi>10.1089/ten.tea.2013.0464</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1937-3341
ispartof Tissue engineering. Part A, 2014-09, Vol.20 (17-18), p.2455-2462
issn 1937-3341
1937-335X
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4161140
source MEDLINE; Alma/SFX Local Collection
subjects Animals
Autografts
Bone Marrow - metabolism
Cartilage
Cartilage, Articular - growth & development
Cartilage, Articular - injuries
Cartilage, Articular - pathology
Cell Differentiation
Cells, Cultured
Cellular biology
Chondrogenesis - physiology
Equipment Design
Extracellular Matrix - transplantation
Mesenchymal Stem Cell Transplantation - instrumentation
Mesenchymal Stem Cell Transplantation - methods
Mesenchymal Stromal Cells - metabolism
Original
Original Articles
Rabbits
Stem cells
Tissue engineering
Tissue Scaffolds
title An Autologous Bone Marrow Mesenchymal Stem Cell–Derived Extracellular Matrix Scaffold Applied with Bone Marrow Stimulation for Cartilage Repair
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-20T01%3A26%3A39IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=An%20Autologous%20Bone%20Marrow%20Mesenchymal%20Stem%20Cell%E2%80%93Derived%20Extracellular%20Matrix%20Scaffold%20Applied%20with%20Bone%20Marrow%20Stimulation%20for%20Cartilage%20Repair&rft.jtitle=Tissue%20engineering.%20Part%20A&rft.au=Tang,%20Cheng&rft.date=2014-09-01&rft.volume=20&rft.issue=17-18&rft.spage=2455&rft.epage=2462&rft.pages=2455-2462&rft.issn=1937-3341&rft.eissn=1937-335X&rft_id=info:doi/10.1089/ten.tea.2013.0464&rft_dat=%3Cproquest_pubme%3E3428916621%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1561318478&rft_id=info:pmid/24666429&rfr_iscdi=true