Direct and Indirect Effects of a Combination of Adipose-Derived Stem Cells and Platelet-Rich Plasma on Bone Regeneration

A key goal for successful bone regeneration is to bridge a bone defect using healing procedures that are stable and durable. Adipose-derived stem cells (ASCs) have the potential to differentiate into bone. Meanwhile, platelet-rich plasma (PRP) is an interesting biological means to repair tissue by i...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Tissue engineering. Part A 2015-03, Vol.21 (5-6), p.895-905
Hauptverfasser: Tajima, Satoshi, Tobita, Morikuni, Orbay, Hakan, Hyakusoku, Hiko, Mizuno, Hiroshi
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 905
container_issue 5-6
container_start_page 895
container_title Tissue engineering. Part A
container_volume 21
creator Tajima, Satoshi
Tobita, Morikuni
Orbay, Hakan
Hyakusoku, Hiko
Mizuno, Hiroshi
description A key goal for successful bone regeneration is to bridge a bone defect using healing procedures that are stable and durable. Adipose-derived stem cells (ASCs) have the potential to differentiate into bone. Meanwhile, platelet-rich plasma (PRP) is an interesting biological means to repair tissue by inducing chemotactic, proliferative, and anabolic cellular responses. This study evaluated bone regeneration using a combination of ASCs and PRP in a rat calvarial defect model. ASCs were isolated from inguinal fat pads of F344 inbred rats, while PRP was prepared from these rats. ASCs were cultured in control medium supplemented with 10% fetal bovine serum or 5% PRP in vitro . After 1 week, levels of growth factors including insulin-like growth factor-1, transforming growth factor-β1, hepatocyte growth factor, and vascular endothelial growth factor in the culture supernatant were measured by enzyme-linked immunosorbent assays. Moreover, the ASC/PRP admixture was transplanted into the rat calvarial defect. Microcomputed tomography, histological, and immunohistochemical (osteopontin and osteocalcin) analyses were performed at 4 and 8 weeks after transplantation. The in vitro study showed that the levels of growth factors secreted by ASCs were significantly increased by the addition of PRP. Transplantation of the ASC/PRP admixture had dramatic effects on bone regeneration overtime in comparison with rats that received other transplants. Furthermore, some ASCs directly differentiated into osteogenic cells in vivo . These findings suggest that the combination of ASCs and PRP has augmentative effects on bone regeneration. The ASC/PRP admixture may be a promising source for the clinical treatment of cranial defects.
doi_str_mv 10.1089/ten.tea.2014.0336
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1768577844</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1768577844</sourcerecordid><originalsourceid>FETCH-LOGICAL-c596t-19c08731ca2993975a6252efe47915cdc24753c86828d1dd3fc7a549d1f6b8f43</originalsourceid><addsrcrecordid>eNqNkT9vFDEQxS1ERELgA9AgSzRp9mKv1__KcEkgUiRQAIlu5bPH4GjXPmwfgm8fby6koEphjWf0e08zegi9oWRFidKnFeKqgln1hA4rwph4ho6oZrJjjH9__vgf6CF6WcotIYIIKV-gw573SnJNj9Cf85DBVmyiw1fR7ZsL71spOHls8DrNmxBNDSkugzMXtqlAdw45_AaHv1SY8Rqmqdx7fJ5MhQlqdxPsz6Urs8FN-T5FwDfwAyLke69X6MCbqcDrh3qMvl1efF1_7K4_fbhan113lmtRO6otUZJRa3qtmZbciLY8eBikptw62w-SM6uE6pWjzjFvpeGDdtSLjfIDO0Yne99tTr92UOo4h2LbviZC2pWRSqG4lGp4AipEPzAm2YK--w-9Tbsc2yELRRlTkspG0T1lcyolgx-3Ocwm_x0pGZcEx5Zge2ZcEhyXBJvm7YPzbjODe1T8i6wBcg8sYxPjFGADuT7B-g4F1amZ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1661338717</pqid></control><display><type>article</type><title>Direct and Indirect Effects of a Combination of Adipose-Derived Stem Cells and Platelet-Rich Plasma on Bone Regeneration</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Tajima, Satoshi ; Tobita, Morikuni ; Orbay, Hakan ; Hyakusoku, Hiko ; Mizuno, Hiroshi</creator><creatorcontrib>Tajima, Satoshi ; Tobita, Morikuni ; Orbay, Hakan ; Hyakusoku, Hiko ; Mizuno, Hiroshi</creatorcontrib><description>A key goal for successful bone regeneration is to bridge a bone defect using healing procedures that are stable and durable. Adipose-derived stem cells (ASCs) have the potential to differentiate into bone. Meanwhile, platelet-rich plasma (PRP) is an interesting biological means to repair tissue by inducing chemotactic, proliferative, and anabolic cellular responses. This study evaluated bone regeneration using a combination of ASCs and PRP in a rat calvarial defect model. ASCs were isolated from inguinal fat pads of F344 inbred rats, while PRP was prepared from these rats. ASCs were cultured in control medium supplemented with 10% fetal bovine serum or 5% PRP in vitro . After 1 week, levels of growth factors including insulin-like growth factor-1, transforming growth factor-β1, hepatocyte growth factor, and vascular endothelial growth factor in the culture supernatant were measured by enzyme-linked immunosorbent assays. Moreover, the ASC/PRP admixture was transplanted into the rat calvarial defect. Microcomputed tomography, histological, and immunohistochemical (osteopontin and osteocalcin) analyses were performed at 4 and 8 weeks after transplantation. The in vitro study showed that the levels of growth factors secreted by ASCs were significantly increased by the addition of PRP. Transplantation of the ASC/PRP admixture had dramatic effects on bone regeneration overtime in comparison with rats that received other transplants. Furthermore, some ASCs directly differentiated into osteogenic cells in vivo . These findings suggest that the combination of ASCs and PRP has augmentative effects on bone regeneration. The ASC/PRP admixture may be a promising source for the clinical treatment of cranial defects.</description><identifier>ISSN: 1937-3341</identifier><identifier>EISSN: 1937-335X</identifier><identifier>DOI: 10.1089/ten.tea.2014.0336</identifier><identifier>PMID: 25287591</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Adipose Tissue - cytology ; Animals ; Bone and Bones - diagnostic imaging ; Bone and Bones - pathology ; Bone and Bones - physiopathology ; Bone Regeneration ; Cells, Cultured ; Green Fluorescent Proteins - metabolism ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins - metabolism ; Male ; Mice, Transgenic ; Original Articles ; Osteocalcin - metabolism ; Osteopontin - metabolism ; Plasma ; Platelet Count ; Platelet-Rich Plasma - metabolism ; Radiography ; Rats, Inbred F344 ; Rats, Nude ; Staining and Labeling ; Stem Cell Transplantation ; Stem cells ; Stem Cells - cytology ; Stem Cells - ultrastructure ; Tissue engineering</subject><ispartof>Tissue engineering. Part A, 2015-03, Vol.21 (5-6), p.895-905</ispartof><rights>2015, Mary Ann Liebert, Inc.</rights><rights>(©) Copyright 2015, Mary Ann Liebert, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c596t-19c08731ca2993975a6252efe47915cdc24753c86828d1dd3fc7a549d1f6b8f43</citedby><cites>FETCH-LOGICAL-c596t-19c08731ca2993975a6252efe47915cdc24753c86828d1dd3fc7a549d1f6b8f43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27915,27916</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25287591$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tajima, Satoshi</creatorcontrib><creatorcontrib>Tobita, Morikuni</creatorcontrib><creatorcontrib>Orbay, Hakan</creatorcontrib><creatorcontrib>Hyakusoku, Hiko</creatorcontrib><creatorcontrib>Mizuno, Hiroshi</creatorcontrib><title>Direct and Indirect Effects of a Combination of Adipose-Derived Stem Cells and Platelet-Rich Plasma on Bone Regeneration</title><title>Tissue engineering. Part A</title><addtitle>Tissue Eng Part A</addtitle><description>A key goal for successful bone regeneration is to bridge a bone defect using healing procedures that are stable and durable. Adipose-derived stem cells (ASCs) have the potential to differentiate into bone. Meanwhile, platelet-rich plasma (PRP) is an interesting biological means to repair tissue by inducing chemotactic, proliferative, and anabolic cellular responses. This study evaluated bone regeneration using a combination of ASCs and PRP in a rat calvarial defect model. ASCs were isolated from inguinal fat pads of F344 inbred rats, while PRP was prepared from these rats. ASCs were cultured in control medium supplemented with 10% fetal bovine serum or 5% PRP in vitro . After 1 week, levels of growth factors including insulin-like growth factor-1, transforming growth factor-β1, hepatocyte growth factor, and vascular endothelial growth factor in the culture supernatant were measured by enzyme-linked immunosorbent assays. Moreover, the ASC/PRP admixture was transplanted into the rat calvarial defect. Microcomputed tomography, histological, and immunohistochemical (osteopontin and osteocalcin) analyses were performed at 4 and 8 weeks after transplantation. The in vitro study showed that the levels of growth factors secreted by ASCs were significantly increased by the addition of PRP. Transplantation of the ASC/PRP admixture had dramatic effects on bone regeneration overtime in comparison with rats that received other transplants. Furthermore, some ASCs directly differentiated into osteogenic cells in vivo . These findings suggest that the combination of ASCs and PRP has augmentative effects on bone regeneration. The ASC/PRP admixture may be a promising source for the clinical treatment of cranial defects.</description><subject>Adipose Tissue - cytology</subject><subject>Animals</subject><subject>Bone and Bones - diagnostic imaging</subject><subject>Bone and Bones - pathology</subject><subject>Bone and Bones - physiopathology</subject><subject>Bone Regeneration</subject><subject>Cells, Cultured</subject><subject>Green Fluorescent Proteins - metabolism</subject><subject>Immunohistochemistry</subject><subject>Intercellular Signaling Peptides and Proteins - metabolism</subject><subject>Male</subject><subject>Mice, Transgenic</subject><subject>Original Articles</subject><subject>Osteocalcin - metabolism</subject><subject>Osteopontin - metabolism</subject><subject>Plasma</subject><subject>Platelet Count</subject><subject>Platelet-Rich Plasma - metabolism</subject><subject>Radiography</subject><subject>Rats, Inbred F344</subject><subject>Rats, Nude</subject><subject>Staining and Labeling</subject><subject>Stem Cell Transplantation</subject><subject>Stem cells</subject><subject>Stem Cells - cytology</subject><subject>Stem Cells - ultrastructure</subject><subject>Tissue engineering</subject><issn>1937-3341</issn><issn>1937-335X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</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>eNqNkT9vFDEQxS1ERELgA9AgSzRp9mKv1__KcEkgUiRQAIlu5bPH4GjXPmwfgm8fby6koEphjWf0e08zegi9oWRFidKnFeKqgln1hA4rwph4ho6oZrJjjH9__vgf6CF6WcotIYIIKV-gw573SnJNj9Cf85DBVmyiw1fR7ZsL71spOHls8DrNmxBNDSkugzMXtqlAdw45_AaHv1SY8Rqmqdx7fJ5MhQlqdxPsz6Urs8FN-T5FwDfwAyLke69X6MCbqcDrh3qMvl1efF1_7K4_fbhan113lmtRO6otUZJRa3qtmZbciLY8eBikptw62w-SM6uE6pWjzjFvpeGDdtSLjfIDO0Yne99tTr92UOo4h2LbviZC2pWRSqG4lGp4AipEPzAm2YK--w-9Tbsc2yELRRlTkspG0T1lcyolgx-3Ocwm_x0pGZcEx5Zge2ZcEhyXBJvm7YPzbjODe1T8i6wBcg8sYxPjFGADuT7B-g4F1amZ</recordid><startdate>20150301</startdate><enddate>20150301</enddate><creator>Tajima, Satoshi</creator><creator>Tobita, Morikuni</creator><creator>Orbay, Hakan</creator><creator>Hyakusoku, Hiko</creator><creator>Mizuno, Hiroshi</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>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20150301</creationdate><title>Direct and Indirect Effects of a Combination of Adipose-Derived Stem Cells and Platelet-Rich Plasma on Bone Regeneration</title><author>Tajima, Satoshi ; Tobita, Morikuni ; Orbay, Hakan ; Hyakusoku, Hiko ; Mizuno, Hiroshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c596t-19c08731ca2993975a6252efe47915cdc24753c86828d1dd3fc7a549d1f6b8f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adipose Tissue - cytology</topic><topic>Animals</topic><topic>Bone and Bones - diagnostic imaging</topic><topic>Bone and Bones - pathology</topic><topic>Bone and Bones - physiopathology</topic><topic>Bone Regeneration</topic><topic>Cells, Cultured</topic><topic>Green Fluorescent Proteins - metabolism</topic><topic>Immunohistochemistry</topic><topic>Intercellular Signaling Peptides and Proteins - metabolism</topic><topic>Male</topic><topic>Mice, Transgenic</topic><topic>Original Articles</topic><topic>Osteocalcin - metabolism</topic><topic>Osteopontin - metabolism</topic><topic>Plasma</topic><topic>Platelet Count</topic><topic>Platelet-Rich Plasma - metabolism</topic><topic>Radiography</topic><topic>Rats, Inbred F344</topic><topic>Rats, Nude</topic><topic>Staining and Labeling</topic><topic>Stem Cell Transplantation</topic><topic>Stem cells</topic><topic>Stem Cells - cytology</topic><topic>Stem Cells - ultrastructure</topic><topic>Tissue engineering</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tajima, Satoshi</creatorcontrib><creatorcontrib>Tobita, Morikuni</creatorcontrib><creatorcontrib>Orbay, Hakan</creatorcontrib><creatorcontrib>Hyakusoku, Hiko</creatorcontrib><creatorcontrib>Mizuno, Hiroshi</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>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Tissue engineering. Part A</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tajima, Satoshi</au><au>Tobita, Morikuni</au><au>Orbay, Hakan</au><au>Hyakusoku, Hiko</au><au>Mizuno, Hiroshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Direct and Indirect Effects of a Combination of Adipose-Derived Stem Cells and Platelet-Rich Plasma on Bone Regeneration</atitle><jtitle>Tissue engineering. Part A</jtitle><addtitle>Tissue Eng Part A</addtitle><date>2015-03-01</date><risdate>2015</risdate><volume>21</volume><issue>5-6</issue><spage>895</spage><epage>905</epage><pages>895-905</pages><issn>1937-3341</issn><eissn>1937-335X</eissn><abstract>A key goal for successful bone regeneration is to bridge a bone defect using healing procedures that are stable and durable. Adipose-derived stem cells (ASCs) have the potential to differentiate into bone. Meanwhile, platelet-rich plasma (PRP) is an interesting biological means to repair tissue by inducing chemotactic, proliferative, and anabolic cellular responses. This study evaluated bone regeneration using a combination of ASCs and PRP in a rat calvarial defect model. ASCs were isolated from inguinal fat pads of F344 inbred rats, while PRP was prepared from these rats. ASCs were cultured in control medium supplemented with 10% fetal bovine serum or 5% PRP in vitro . After 1 week, levels of growth factors including insulin-like growth factor-1, transforming growth factor-β1, hepatocyte growth factor, and vascular endothelial growth factor in the culture supernatant were measured by enzyme-linked immunosorbent assays. Moreover, the ASC/PRP admixture was transplanted into the rat calvarial defect. Microcomputed tomography, histological, and immunohistochemical (osteopontin and osteocalcin) analyses were performed at 4 and 8 weeks after transplantation. The in vitro study showed that the levels of growth factors secreted by ASCs were significantly increased by the addition of PRP. Transplantation of the ASC/PRP admixture had dramatic effects on bone regeneration overtime in comparison with rats that received other transplants. Furthermore, some ASCs directly differentiated into osteogenic cells in vivo . These findings suggest that the combination of ASCs and PRP has augmentative effects on bone regeneration. The ASC/PRP admixture may be a promising source for the clinical treatment of cranial defects.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>25287591</pmid><doi>10.1089/ten.tea.2014.0336</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1937-3341
ispartof Tissue engineering. Part A, 2015-03, Vol.21 (5-6), p.895-905
issn 1937-3341
1937-335X
language eng
recordid cdi_proquest_miscellaneous_1768577844
source MEDLINE; Alma/SFX Local Collection
subjects Adipose Tissue - cytology
Animals
Bone and Bones - diagnostic imaging
Bone and Bones - pathology
Bone and Bones - physiopathology
Bone Regeneration
Cells, Cultured
Green Fluorescent Proteins - metabolism
Immunohistochemistry
Intercellular Signaling Peptides and Proteins - metabolism
Male
Mice, Transgenic
Original Articles
Osteocalcin - metabolism
Osteopontin - metabolism
Plasma
Platelet Count
Platelet-Rich Plasma - metabolism
Radiography
Rats, Inbred F344
Rats, Nude
Staining and Labeling
Stem Cell Transplantation
Stem cells
Stem Cells - cytology
Stem Cells - ultrastructure
Tissue engineering
title Direct and Indirect Effects of a Combination of Adipose-Derived Stem Cells and Platelet-Rich Plasma on Bone Regeneration
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T03%3A44%3A32IST&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=Direct%20and%20Indirect%20Effects%20of%20a%20Combination%20of%20Adipose-Derived%20Stem%20Cells%20and%20Platelet-Rich%20Plasma%20on%20Bone%20Regeneration&rft.jtitle=Tissue%20engineering.%20Part%20A&rft.au=Tajima,%20Satoshi&rft.date=2015-03-01&rft.volume=21&rft.issue=5-6&rft.spage=895&rft.epage=905&rft.pages=895-905&rft.issn=1937-3341&rft.eissn=1937-335X&rft_id=info:doi/10.1089/ten.tea.2014.0336&rft_dat=%3Cproquest_cross%3E1768577844%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=1661338717&rft_id=info:pmid/25287591&rfr_iscdi=true