Sustained release of GDF5 from a designed coacervate attenuates disc degeneration in a rat model
[Display omitted] Low back pain is often caused by intervertebral disc degeneration, which is characterized by nucleus pulposus (NP) and extracellular matrix (ECM) degeneration. Human adipose-derived stem cells (hADSCs) induced by growth and differentiation factor-5 (GDF5) can differentiate into an...
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| Veröffentlicht in: | Acta biomaterialia 2019-03, Vol.86, p.300-311 |
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| creator | Zhu, Jian Xia, Kaishun Yu, Wei Wang, Yitian Hua, Jianming Liu, Bing Gong, Zhe Wang, Junjie Xu, Ankai You, Zhengwei Chen, Qixin Li, Fangcai Tao, Huimin Liang, Chengzhen |
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Low back pain is often caused by intervertebral disc degeneration, which is characterized by nucleus pulposus (NP) and extracellular matrix (ECM) degeneration. Human adipose-derived stem cells (hADSCs) induced by growth and differentiation factor-5 (GDF5) can differentiate into an NP-like phenotype. Although stem cell-based therapy with prolonged exposure to growth factors is regarded as a promising treatment, the efficacy of this approach in attenuating the disc degeneration process is limited by the short lifespan of growth factors. In our study, a unique growth factor delivery vehicle composed of heparin and the synthetic polycation poly(ethylene argininylaspartate diglyceride) (PEAD) was used to sustain GDF5 release. The results showed that sustained release of GDF5 by the PEAD:heparin delivery system promoted hADSC differentiation to an NP-like phenotype in vitro. After injection of the PEAD:heparin:GDF5 delivery platform and hADSCs into intervertebral spaces of coccygeal (Co) vertebrae Co7/Co8 and Co8/Co9 of the rat, the disc height, water content, and structure of the NPs decreased more slowly than other treatment groups. This new strategy may be used as an alternative treatment for attenuating intervertebral disc degeneration with hADSCs without the need for gene therapy.
Low back pain is often caused by intervertebral disc degeneration, which is characterized by nucleus pulposus (NP) and extracellular matrix (ECM) degeneration. Human adipose-derived stem cells (hADSCs) induced by growth and differentiation factor-5 (GDF-5) can differentiate into an NP-like phenotype. Although stem cell-based therapy with prolonged exposure to growth factor is regarded as a promising treatment, the efficacy of this approach in the disc regeneration process is limited by the short life of growth factors. In our study, a unique growth factor delivery vehicle comprised of heparin and the synthetic polycation poly(ethylene argininylaspartate diglyceride) (PEAD) was used to sustain the release of GDF-5. Numerous groups have explored IDD regeneration methods in vitro and in vivo. Our study differs in that GDF5 was incorporated into a vehicle through charge attraction and exhibited a sustained release profile. Moreover, GDF-5 seeded coacervate combined with hADSC injection could be a minimally invasive approach for tissue engineering that is suitable for clinical application. We investigated the stimulatory effects of our GDF-5 seeded coacervate on the d |
| doi_str_mv | 10.1016/j.actbio.2019.01.028 |
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Low back pain is often caused by intervertebral disc degeneration, which is characterized by nucleus pulposus (NP) and extracellular matrix (ECM) degeneration. Human adipose-derived stem cells (hADSCs) induced by growth and differentiation factor-5 (GDF5) can differentiate into an NP-like phenotype. Although stem cell-based therapy with prolonged exposure to growth factors is regarded as a promising treatment, the efficacy of this approach in attenuating the disc degeneration process is limited by the short lifespan of growth factors. In our study, a unique growth factor delivery vehicle composed of heparin and the synthetic polycation poly(ethylene argininylaspartate diglyceride) (PEAD) was used to sustain GDF5 release. The results showed that sustained release of GDF5 by the PEAD:heparin delivery system promoted hADSC differentiation to an NP-like phenotype in vitro. After injection of the PEAD:heparin:GDF5 delivery platform and hADSCs into intervertebral spaces of coccygeal (Co) vertebrae Co7/Co8 and Co8/Co9 of the rat, the disc height, water content, and structure of the NPs decreased more slowly than other treatment groups. This new strategy may be used as an alternative treatment for attenuating intervertebral disc degeneration with hADSCs without the need for gene therapy.
Low back pain is often caused by intervertebral disc degeneration, which is characterized by nucleus pulposus (NP) and extracellular matrix (ECM) degeneration. Human adipose-derived stem cells (hADSCs) induced by growth and differentiation factor-5 (GDF-5) can differentiate into an NP-like phenotype. Although stem cell-based therapy with prolonged exposure to growth factor is regarded as a promising treatment, the efficacy of this approach in the disc regeneration process is limited by the short life of growth factors. In our study, a unique growth factor delivery vehicle comprised of heparin and the synthetic polycation poly(ethylene argininylaspartate diglyceride) (PEAD) was used to sustain the release of GDF-5. Numerous groups have explored IDD regeneration methods in vitro and in vivo. Our study differs in that GDF5 was incorporated into a vehicle through charge attraction and exhibited a sustained release profile. Moreover, GDF-5 seeded coacervate combined with hADSC injection could be a minimally invasive approach for tissue engineering that is suitable for clinical application. We investigated the stimulatory effects of our GDF-5 seeded coacervate on the differentiation of ADSCs in vitro and the reparative effect of the delivery system on degenerated NP in vivo.</description><identifier>ISSN: 1742-7061</identifier><identifier>EISSN: 1878-7568</identifier><identifier>DOI: 10.1016/j.actbio.2019.01.028</identifier><identifier>PMID: 30660009</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Attenuation ; Cell Differentiation - drug effects ; Cell Proliferation - drug effects ; Collagen Type II - metabolism ; Controlled release ; Degeneration ; Delayed-Action Preparations - pharmacology ; Delayed-Action Preparations - therapeutic use ; Differentiation ; Disease Models, Animal ; Extracellular matrix ; Gene Expression Regulation - drug effects ; Gene therapy ; Growth differentiation factor 5 ; Growth Differentiation Factor 5 - pharmacology ; Growth Differentiation Factor 5 - therapeutic use ; Growth factor therapy ; Growth factors ; Heparin ; Human adipose-derived stem cells ; Humans ; Intervertebral disc ; Intervertebral Disc - diagnostic imaging ; Intervertebral Disc - pathology ; Intervertebral Disc Degeneration - diagnostic imaging ; Intervertebral Disc Degeneration - drug therapy ; Intervertebral Disc Degeneration - pathology ; Intervertebral discs ; Life span ; Low back pain ; Magnetic Resonance Imaging ; Moisture content ; Nuclei (cytology) ; Nucleus pulposus ; Nucleus Pulposus - pathology ; Pain ; Peptides - chemical synthesis ; Peptides - chemistry ; Phenotype ; Phenotypes ; Polyelectrolytes ; Polyesters - chemical synthesis ; Polyesters - chemistry ; Rats, Sprague-Dawley ; Spine ; Stem cell transplantation ; Stem cells ; Stem Cells - cytology ; Stem Cells - drug effects ; Stem Cells - metabolism ; Sustained release ; Vertebrae ; Water content</subject><ispartof>Acta biomaterialia, 2019-03, Vol.86, p.300-311</ispartof><rights>2019 Acta Materialia Inc.</rights><rights>Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier BV Mar 1, 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-a536a1469142bc8c97d004f005bffcf4a17ed56a1cadd393810e55665354094d3</citedby><cites>FETCH-LOGICAL-c390t-a536a1469142bc8c97d004f005bffcf4a17ed56a1cadd393810e55665354094d3</cites><orcidid>0000-0003-1038-1321 ; 0000-0002-2948-2141</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.actbio.2019.01.028$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30660009$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhu, Jian</creatorcontrib><creatorcontrib>Xia, Kaishun</creatorcontrib><creatorcontrib>Yu, Wei</creatorcontrib><creatorcontrib>Wang, Yitian</creatorcontrib><creatorcontrib>Hua, Jianming</creatorcontrib><creatorcontrib>Liu, Bing</creatorcontrib><creatorcontrib>Gong, Zhe</creatorcontrib><creatorcontrib>Wang, Junjie</creatorcontrib><creatorcontrib>Xu, Ankai</creatorcontrib><creatorcontrib>You, Zhengwei</creatorcontrib><creatorcontrib>Chen, Qixin</creatorcontrib><creatorcontrib>Li, Fangcai</creatorcontrib><creatorcontrib>Tao, Huimin</creatorcontrib><creatorcontrib>Liang, Chengzhen</creatorcontrib><title>Sustained release of GDF5 from a designed coacervate attenuates disc degeneration in a rat model</title><title>Acta biomaterialia</title><addtitle>Acta Biomater</addtitle><description>[Display omitted]
Low back pain is often caused by intervertebral disc degeneration, which is characterized by nucleus pulposus (NP) and extracellular matrix (ECM) degeneration. Human adipose-derived stem cells (hADSCs) induced by growth and differentiation factor-5 (GDF5) can differentiate into an NP-like phenotype. Although stem cell-based therapy with prolonged exposure to growth factors is regarded as a promising treatment, the efficacy of this approach in attenuating the disc degeneration process is limited by the short lifespan of growth factors. In our study, a unique growth factor delivery vehicle composed of heparin and the synthetic polycation poly(ethylene argininylaspartate diglyceride) (PEAD) was used to sustain GDF5 release. The results showed that sustained release of GDF5 by the PEAD:heparin delivery system promoted hADSC differentiation to an NP-like phenotype in vitro. After injection of the PEAD:heparin:GDF5 delivery platform and hADSCs into intervertebral spaces of coccygeal (Co) vertebrae Co7/Co8 and Co8/Co9 of the rat, the disc height, water content, and structure of the NPs decreased more slowly than other treatment groups. This new strategy may be used as an alternative treatment for attenuating intervertebral disc degeneration with hADSCs without the need for gene therapy.
Low back pain is often caused by intervertebral disc degeneration, which is characterized by nucleus pulposus (NP) and extracellular matrix (ECM) degeneration. Human adipose-derived stem cells (hADSCs) induced by growth and differentiation factor-5 (GDF-5) can differentiate into an NP-like phenotype. Although stem cell-based therapy with prolonged exposure to growth factor is regarded as a promising treatment, the efficacy of this approach in the disc regeneration process is limited by the short life of growth factors. In our study, a unique growth factor delivery vehicle comprised of heparin and the synthetic polycation poly(ethylene argininylaspartate diglyceride) (PEAD) was used to sustain the release of GDF-5. Numerous groups have explored IDD regeneration methods in vitro and in vivo. Our study differs in that GDF5 was incorporated into a vehicle through charge attraction and exhibited a sustained release profile. Moreover, GDF-5 seeded coacervate combined with hADSC injection could be a minimally invasive approach for tissue engineering that is suitable for clinical application. We investigated the stimulatory effects of our GDF-5 seeded coacervate on the differentiation of ADSCs in vitro and the reparative effect of the delivery system on degenerated NP in vivo.</description><subject>Animals</subject><subject>Attenuation</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Collagen Type II - metabolism</subject><subject>Controlled release</subject><subject>Degeneration</subject><subject>Delayed-Action Preparations - pharmacology</subject><subject>Delayed-Action Preparations - therapeutic use</subject><subject>Differentiation</subject><subject>Disease Models, Animal</subject><subject>Extracellular matrix</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Gene therapy</subject><subject>Growth differentiation factor 5</subject><subject>Growth Differentiation Factor 5 - pharmacology</subject><subject>Growth Differentiation Factor 5 - therapeutic use</subject><subject>Growth factor therapy</subject><subject>Growth factors</subject><subject>Heparin</subject><subject>Human adipose-derived stem cells</subject><subject>Humans</subject><subject>Intervertebral disc</subject><subject>Intervertebral Disc - diagnostic imaging</subject><subject>Intervertebral Disc - pathology</subject><subject>Intervertebral Disc Degeneration - diagnostic imaging</subject><subject>Intervertebral Disc Degeneration - drug therapy</subject><subject>Intervertebral Disc Degeneration - pathology</subject><subject>Intervertebral discs</subject><subject>Life span</subject><subject>Low back pain</subject><subject>Magnetic Resonance Imaging</subject><subject>Moisture content</subject><subject>Nuclei (cytology)</subject><subject>Nucleus pulposus</subject><subject>Nucleus Pulposus - pathology</subject><subject>Pain</subject><subject>Peptides - chemical synthesis</subject><subject>Peptides - chemistry</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>Polyelectrolytes</subject><subject>Polyesters - chemical synthesis</subject><subject>Polyesters - chemistry</subject><subject>Rats, Sprague-Dawley</subject><subject>Spine</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Stem Cells - cytology</subject><subject>Stem Cells - drug effects</subject><subject>Stem Cells - metabolism</subject><subject>Sustained release</subject><subject>Vertebrae</subject><subject>Water content</subject><issn>1742-7061</issn><issn>1878-7568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUtr3TAQhUVpaR7tPyhB0E03dkfWw9YmUNK8INBF2rWqK42DLraVSHKg_z663CSLLrKaA_Od0WgOIV8YtAyY-r5trSubENsOmG6BtdAN78ghG_qh6aUa3lfdi67pQbEDcpTzFoAPrBs-kgMOSgGAPiR_b9dcbFjQ04QT2ow0jvTy54WkY4oztdRjDne7vovWYXq0BaktBZe1qkx9yK4yd7hgsiXEhYaluqqmc_Q4fSIfRjtl_Pxcj8mfi_PfZ1fNza_L67MfN43jGkpjJVeWCaWZ6DZucLr3AGIEkJtxdKOwrEcvK-Ks91zXjwBKqZTkUoAWnh-Tb_u59yk-rJiLmetmOE12wbhm07FeC2CDhIp-_Q_dxjUtdbtKacYF41JXSuwpl2LOCUdzn8Js0z_DwOwSMFuzT8DsEjDATE2g2k6eh6-bGf2r6eXkFTjdA1iv8RgwmewCLg59SOiK8TG8_cITJbGXbQ</recordid><startdate>20190301</startdate><enddate>20190301</enddate><creator>Zhu, Jian</creator><creator>Xia, Kaishun</creator><creator>Yu, Wei</creator><creator>Wang, Yitian</creator><creator>Hua, Jianming</creator><creator>Liu, Bing</creator><creator>Gong, Zhe</creator><creator>Wang, Junjie</creator><creator>Xu, Ankai</creator><creator>You, Zhengwei</creator><creator>Chen, Qixin</creator><creator>Li, Fangcai</creator><creator>Tao, Huimin</creator><creator>Liang, Chengzhen</creator><general>Elsevier Ltd</general><general>Elsevier BV</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>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1038-1321</orcidid><orcidid>https://orcid.org/0000-0002-2948-2141</orcidid></search><sort><creationdate>20190301</creationdate><title>Sustained release of GDF5 from a designed coacervate attenuates disc degeneration in a rat model</title><author>Zhu, Jian ; Xia, Kaishun ; Yu, Wei ; Wang, Yitian ; Hua, Jianming ; Liu, Bing ; Gong, Zhe ; Wang, Junjie ; Xu, Ankai ; You, Zhengwei ; Chen, Qixin ; Li, Fangcai ; Tao, Huimin ; Liang, Chengzhen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-a536a1469142bc8c97d004f005bffcf4a17ed56a1cadd393810e55665354094d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Attenuation</topic><topic>Cell Differentiation - 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Academic</collection><jtitle>Acta biomaterialia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhu, Jian</au><au>Xia, Kaishun</au><au>Yu, Wei</au><au>Wang, Yitian</au><au>Hua, Jianming</au><au>Liu, Bing</au><au>Gong, Zhe</au><au>Wang, Junjie</au><au>Xu, Ankai</au><au>You, Zhengwei</au><au>Chen, Qixin</au><au>Li, Fangcai</au><au>Tao, Huimin</au><au>Liang, Chengzhen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sustained release of GDF5 from a designed coacervate attenuates disc degeneration in a rat model</atitle><jtitle>Acta biomaterialia</jtitle><addtitle>Acta Biomater</addtitle><date>2019-03-01</date><risdate>2019</risdate><volume>86</volume><spage>300</spage><epage>311</epage><pages>300-311</pages><issn>1742-7061</issn><eissn>1878-7568</eissn><abstract>[Display omitted]
Low back pain is often caused by intervertebral disc degeneration, which is characterized by nucleus pulposus (NP) and extracellular matrix (ECM) degeneration. Human adipose-derived stem cells (hADSCs) induced by growth and differentiation factor-5 (GDF5) can differentiate into an NP-like phenotype. Although stem cell-based therapy with prolonged exposure to growth factors is regarded as a promising treatment, the efficacy of this approach in attenuating the disc degeneration process is limited by the short lifespan of growth factors. In our study, a unique growth factor delivery vehicle composed of heparin and the synthetic polycation poly(ethylene argininylaspartate diglyceride) (PEAD) was used to sustain GDF5 release. The results showed that sustained release of GDF5 by the PEAD:heparin delivery system promoted hADSC differentiation to an NP-like phenotype in vitro. After injection of the PEAD:heparin:GDF5 delivery platform and hADSCs into intervertebral spaces of coccygeal (Co) vertebrae Co7/Co8 and Co8/Co9 of the rat, the disc height, water content, and structure of the NPs decreased more slowly than other treatment groups. This new strategy may be used as an alternative treatment for attenuating intervertebral disc degeneration with hADSCs without the need for gene therapy.
Low back pain is often caused by intervertebral disc degeneration, which is characterized by nucleus pulposus (NP) and extracellular matrix (ECM) degeneration. Human adipose-derived stem cells (hADSCs) induced by growth and differentiation factor-5 (GDF-5) can differentiate into an NP-like phenotype. Although stem cell-based therapy with prolonged exposure to growth factor is regarded as a promising treatment, the efficacy of this approach in the disc regeneration process is limited by the short life of growth factors. In our study, a unique growth factor delivery vehicle comprised of heparin and the synthetic polycation poly(ethylene argininylaspartate diglyceride) (PEAD) was used to sustain the release of GDF-5. Numerous groups have explored IDD regeneration methods in vitro and in vivo. Our study differs in that GDF5 was incorporated into a vehicle through charge attraction and exhibited a sustained release profile. Moreover, GDF-5 seeded coacervate combined with hADSC injection could be a minimally invasive approach for tissue engineering that is suitable for clinical application. We investigated the stimulatory effects of our GDF-5 seeded coacervate on the differentiation of ADSCs in vitro and the reparative effect of the delivery system on degenerated NP in vivo.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>30660009</pmid><doi>10.1016/j.actbio.2019.01.028</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-1038-1321</orcidid><orcidid>https://orcid.org/0000-0002-2948-2141</orcidid></addata></record> |
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| identifier | ISSN: 1742-7061 |
| ispartof | Acta biomaterialia, 2019-03, Vol.86, p.300-311 |
| issn | 1742-7061 1878-7568 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2179401850 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Attenuation Cell Differentiation - drug effects Cell Proliferation - drug effects Collagen Type II - metabolism Controlled release Degeneration Delayed-Action Preparations - pharmacology Delayed-Action Preparations - therapeutic use Differentiation Disease Models, Animal Extracellular matrix Gene Expression Regulation - drug effects Gene therapy Growth differentiation factor 5 Growth Differentiation Factor 5 - pharmacology Growth Differentiation Factor 5 - therapeutic use Growth factor therapy Growth factors Heparin Human adipose-derived stem cells Humans Intervertebral disc Intervertebral Disc - diagnostic imaging Intervertebral Disc - pathology Intervertebral Disc Degeneration - diagnostic imaging Intervertebral Disc Degeneration - drug therapy Intervertebral Disc Degeneration - pathology Intervertebral discs Life span Low back pain Magnetic Resonance Imaging Moisture content Nuclei (cytology) Nucleus pulposus Nucleus Pulposus - pathology Pain Peptides - chemical synthesis Peptides - chemistry Phenotype Phenotypes Polyelectrolytes Polyesters - chemical synthesis Polyesters - chemistry Rats, Sprague-Dawley Spine Stem cell transplantation Stem cells Stem Cells - cytology Stem Cells - drug effects Stem Cells - metabolism Sustained release Vertebrae Water content |
| title | Sustained release of GDF5 from a designed coacervate attenuates disc degeneration in a rat model |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T10%3A04%3A35IST&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=Sustained%20release%20of%20GDF5%20from%20a%20designed%20coacervate%20attenuates%20disc%20degeneration%20in%20a%20rat%20model&rft.jtitle=Acta%20biomaterialia&rft.au=Zhu,%20Jian&rft.date=2019-03-01&rft.volume=86&rft.spage=300&rft.epage=311&rft.pages=300-311&rft.issn=1742-7061&rft.eissn=1878-7568&rft_id=info:doi/10.1016/j.actbio.2019.01.028&rft_dat=%3Cproquest_cross%3E2191341359%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=2191341359&rft_id=info:pmid/30660009&rft_els_id=S1742706119300480&rfr_iscdi=true |