Osteogenic differentiation of mesenchymal stromal cells in two-dimensional and three-dimensional cultures without animal serum

Bone marrow-derived mesenchymal stromal cells (MSCs) have been intensely studied for the purpose of developing solutions for clinical tissue engineering. Autologous MSCs can potentially be used to replace tissue defects, but the procedure also carries risks such as immunization and xenogeneic infect...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Stem cell research & therapy 2015-09, Vol.6 (1), p.167-167, Article 167
Hauptverfasser: Castrén, Eeva, Sillat, Tarvo, Oja, Sofia, Noro, Ariel, Laitinen, Anita, Konttinen, Yrjö T, Lehenkari, Petri, Hukkanen, Mika, Korhonen, Matti
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 167
container_issue 1
container_start_page 167
container_title Stem cell research & therapy
container_volume 6
creator Castrén, Eeva
Sillat, Tarvo
Oja, Sofia
Noro, Ariel
Laitinen, Anita
Konttinen, Yrjö T
Lehenkari, Petri
Hukkanen, Mika
Korhonen, Matti
description Bone marrow-derived mesenchymal stromal cells (MSCs) have been intensely studied for the purpose of developing solutions for clinical tissue engineering. Autologous MSCs can potentially be used to replace tissue defects, but the procedure also carries risks such as immunization and xenogeneic infection. Replacement of the commonly used fetal calf serum (FCS) with human platelet lysate and plasma (PLP) to support cell growth may reduce some of these risks. Altered media could, however, influence stem cell differentiation and we address this experimentally. We examined human MSC differentiation into the osteoblast lineage using in vitro two- and three-dimensional cultures with PLP or FCS as cell culture medium supplements. Differentiation was followed by quantitative polymerase chain reaction, and alkaline phosphatase activity, matrix formation and matrix calcium content were quantified. Three-dimensional culture, where human MSCs were grown on collagen sponges, markedly stimulated osteoblast differentiation; a fourfold increase in calcium deposition could be observed in both PLP and FCS groups. PLP-grown cells showed robust osteogenic differentiation both in two- and three-dimensional MSC cultures. The calcium content of the matrix in the two-dimensional PLP group at day 14 was 2.2-fold higher in comparison to the FCS group (p 
doi_str_mv 10.1186/s13287-015-0162-6
format Article
fullrecord <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4562352</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A541635125</galeid><sourcerecordid>A541635125</sourcerecordid><originalsourceid>FETCH-LOGICAL-c559t-df7f5e2467bd3afe7e6dc4da48133ee877e38050060ffd8a222b9b0a8029a1fe3</originalsourceid><addsrcrecordid>eNptkttqFTEUhgdRbKl9AG9kQBC9mJrDJJm5EUrxUCgUPFyH7MzKnpSZpObQ2huf3Yy71j1iQlgh-dafZOWvqucYnWDc8bcRU9KJBmFWBicNf1QdYsFEwxkmj_fmB9VxjFeoNEoR4u3T6oBw2rK-J4fVz8uYwG_BWV0P1hgI4JJVyXpXe1PPEMHp8W5WUx1T8EvUME2xtq5Ot74Z7AwuFrpsKDfUaQwAq1Wdp5QDxPrWptHnVDD7Ww5Cnp9VT4yaIhzfx6Pq24f3X88-NReXH8_PTi8azVifmsEIw4C0XGwGqgwI4INuB9V2mFKATgigHWLldciYoVOEkE2_QapDpFfYAD2q3u10r_NmhkGXRwY1yetQrhLupFdWrnecHeXW38iWcUIZKQKv7wWC_54hJjnbuFRCOfA5Siww4ozhvi_oy3_QK59DKcVCCVIu2gn0l9qqCaR1xpdz9SIqT1mLOS0_xwp18h-q9AFmq70DY8v6KuHNKqEwCX6krcoxyvMvn9fsqz12BDWlMfopL58f1yDegTr4GAOYh8JhJBczyp0ZZTGjXMwoecl5sV_xh4w_1qO_AFLB2uI</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1772380870</pqid></control><display><type>article</type><title>Osteogenic differentiation of mesenchymal stromal cells in two-dimensional and three-dimensional cultures without animal serum</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>PubMed Central Open Access</source><source>Springer Nature OA Free Journals</source><source>Springer Nature - Complete Springer Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Castrén, Eeva ; Sillat, Tarvo ; Oja, Sofia ; Noro, Ariel ; Laitinen, Anita ; Konttinen, Yrjö T ; Lehenkari, Petri ; Hukkanen, Mika ; Korhonen, Matti</creator><creatorcontrib>Castrén, Eeva ; Sillat, Tarvo ; Oja, Sofia ; Noro, Ariel ; Laitinen, Anita ; Konttinen, Yrjö T ; Lehenkari, Petri ; Hukkanen, Mika ; Korhonen, Matti</creatorcontrib><description>Bone marrow-derived mesenchymal stromal cells (MSCs) have been intensely studied for the purpose of developing solutions for clinical tissue engineering. Autologous MSCs can potentially be used to replace tissue defects, but the procedure also carries risks such as immunization and xenogeneic infection. Replacement of the commonly used fetal calf serum (FCS) with human platelet lysate and plasma (PLP) to support cell growth may reduce some of these risks. Altered media could, however, influence stem cell differentiation and we address this experimentally. We examined human MSC differentiation into the osteoblast lineage using in vitro two- and three-dimensional cultures with PLP or FCS as cell culture medium supplements. Differentiation was followed by quantitative polymerase chain reaction, and alkaline phosphatase activity, matrix formation and matrix calcium content were quantified. Three-dimensional culture, where human MSCs were grown on collagen sponges, markedly stimulated osteoblast differentiation; a fourfold increase in calcium deposition could be observed in both PLP and FCS groups. PLP-grown cells showed robust osteogenic differentiation both in two- and three-dimensional MSC cultures. The calcium content of the matrix in the two-dimensional PLP group at day 14 was 2.2-fold higher in comparison to the FCS group (p &lt; 0.0001), and at day 21 it was still 1.3-fold higher (p &lt; 0.001), suggesting earlier calcium accumulation to the matrix in the PLP group. This was supported by stronger Alizarin Red staining in the PLP group at day 14. In two-dimesional PLP cultures, cellular proliferation appeared to decrease during later stages of differentiation, while in the FCS group the number of cells increased throughout the experiment. In three-dimensional experiments, the PLP and FCS groups behaved more congruently, except for the alkaline phosphatase activity and mRNA levels which were markedly increased by PLP. Human PLP was at least equal to FCS in supporting osteogenic differentiation of human MSCs in two- and three-dimensional conditions; however, proliferation was inferior. As PLP is free of animal components, and thus represents reduced risk for xenogeneic infection, its use for human MSC-induced bone repair in the clinic by the three-dimensional live implants presented here appears a promising therapy option.</description><identifier>ISSN: 1757-6512</identifier><identifier>EISSN: 1757-6512</identifier><identifier>DOI: 10.1186/s13287-015-0162-6</identifier><identifier>PMID: 26345992</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Adult ; Analysis ; Cattle ; Cell differentiation ; Cells, Cultured ; Collagen ; Genetic aspects ; Health aspects ; Humans ; Infection ; Mesenchymal Stromal Cells - cytology ; Osteoblasts - cytology ; Osteogenesis ; Phosphatases ; Physiological aspects ; Primary Cell Culture - methods ; Serum ; Stem cells ; Tissue engineering</subject><ispartof>Stem cell research &amp; therapy, 2015-09, Vol.6 (1), p.167-167, Article 167</ispartof><rights>COPYRIGHT 2015 BioMed Central Ltd.</rights><rights>Copyright BioMed Central 2015</rights><rights>Castrén et al. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c559t-df7f5e2467bd3afe7e6dc4da48133ee877e38050060ffd8a222b9b0a8029a1fe3</citedby><cites>FETCH-LOGICAL-c559t-df7f5e2467bd3afe7e6dc4da48133ee877e38050060ffd8a222b9b0a8029a1fe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562352/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562352/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27903,27904,53770,53772</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26345992$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Castrén, Eeva</creatorcontrib><creatorcontrib>Sillat, Tarvo</creatorcontrib><creatorcontrib>Oja, Sofia</creatorcontrib><creatorcontrib>Noro, Ariel</creatorcontrib><creatorcontrib>Laitinen, Anita</creatorcontrib><creatorcontrib>Konttinen, Yrjö T</creatorcontrib><creatorcontrib>Lehenkari, Petri</creatorcontrib><creatorcontrib>Hukkanen, Mika</creatorcontrib><creatorcontrib>Korhonen, Matti</creatorcontrib><title>Osteogenic differentiation of mesenchymal stromal cells in two-dimensional and three-dimensional cultures without animal serum</title><title>Stem cell research &amp; therapy</title><addtitle>Stem Cell Res Ther</addtitle><description>Bone marrow-derived mesenchymal stromal cells (MSCs) have been intensely studied for the purpose of developing solutions for clinical tissue engineering. Autologous MSCs can potentially be used to replace tissue defects, but the procedure also carries risks such as immunization and xenogeneic infection. Replacement of the commonly used fetal calf serum (FCS) with human platelet lysate and plasma (PLP) to support cell growth may reduce some of these risks. Altered media could, however, influence stem cell differentiation and we address this experimentally. We examined human MSC differentiation into the osteoblast lineage using in vitro two- and three-dimensional cultures with PLP or FCS as cell culture medium supplements. Differentiation was followed by quantitative polymerase chain reaction, and alkaline phosphatase activity, matrix formation and matrix calcium content were quantified. Three-dimensional culture, where human MSCs were grown on collagen sponges, markedly stimulated osteoblast differentiation; a fourfold increase in calcium deposition could be observed in both PLP and FCS groups. PLP-grown cells showed robust osteogenic differentiation both in two- and three-dimensional MSC cultures. The calcium content of the matrix in the two-dimensional PLP group at day 14 was 2.2-fold higher in comparison to the FCS group (p &lt; 0.0001), and at day 21 it was still 1.3-fold higher (p &lt; 0.001), suggesting earlier calcium accumulation to the matrix in the PLP group. This was supported by stronger Alizarin Red staining in the PLP group at day 14. In two-dimesional PLP cultures, cellular proliferation appeared to decrease during later stages of differentiation, while in the FCS group the number of cells increased throughout the experiment. In three-dimensional experiments, the PLP and FCS groups behaved more congruently, except for the alkaline phosphatase activity and mRNA levels which were markedly increased by PLP. Human PLP was at least equal to FCS in supporting osteogenic differentiation of human MSCs in two- and three-dimensional conditions; however, proliferation was inferior. As PLP is free of animal components, and thus represents reduced risk for xenogeneic infection, its use for human MSC-induced bone repair in the clinic by the three-dimensional live implants presented here appears a promising therapy option.</description><subject>Adult</subject><subject>Analysis</subject><subject>Cattle</subject><subject>Cell differentiation</subject><subject>Cells, Cultured</subject><subject>Collagen</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Infection</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Osteoblasts - cytology</subject><subject>Osteogenesis</subject><subject>Phosphatases</subject><subject>Physiological aspects</subject><subject>Primary Cell Culture - methods</subject><subject>Serum</subject><subject>Stem cells</subject><subject>Tissue engineering</subject><issn>1757-6512</issn><issn>1757-6512</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>eNptkttqFTEUhgdRbKl9AG9kQBC9mJrDJJm5EUrxUCgUPFyH7MzKnpSZpObQ2huf3Yy71j1iQlgh-dafZOWvqucYnWDc8bcRU9KJBmFWBicNf1QdYsFEwxkmj_fmB9VxjFeoNEoR4u3T6oBw2rK-J4fVz8uYwG_BWV0P1hgI4JJVyXpXe1PPEMHp8W5WUx1T8EvUME2xtq5Ot74Z7AwuFrpsKDfUaQwAq1Wdp5QDxPrWptHnVDD7Ww5Cnp9VT4yaIhzfx6Pq24f3X88-NReXH8_PTi8azVifmsEIw4C0XGwGqgwI4INuB9V2mFKATgigHWLldciYoVOEkE2_QapDpFfYAD2q3u10r_NmhkGXRwY1yetQrhLupFdWrnecHeXW38iWcUIZKQKv7wWC_54hJjnbuFRCOfA5Siww4ozhvi_oy3_QK59DKcVCCVIu2gn0l9qqCaR1xpdz9SIqT1mLOS0_xwp18h-q9AFmq70DY8v6KuHNKqEwCX6krcoxyvMvn9fsqz12BDWlMfopL58f1yDegTr4GAOYh8JhJBczyp0ZZTGjXMwoecl5sV_xh4w_1qO_AFLB2uI</recordid><startdate>20150907</startdate><enddate>20150907</enddate><creator>Castrén, Eeva</creator><creator>Sillat, Tarvo</creator><creator>Oja, Sofia</creator><creator>Noro, Ariel</creator><creator>Laitinen, Anita</creator><creator>Konttinen, Yrjö T</creator><creator>Lehenkari, Petri</creator><creator>Hukkanen, Mika</creator><creator>Korhonen, Matti</creator><general>BioMed Central Ltd</general><general>BioMed Central</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>ISR</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</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>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150907</creationdate><title>Osteogenic differentiation of mesenchymal stromal cells in two-dimensional and three-dimensional cultures without animal serum</title><author>Castrén, Eeva ; Sillat, Tarvo ; Oja, Sofia ; Noro, Ariel ; Laitinen, Anita ; Konttinen, Yrjö T ; Lehenkari, Petri ; Hukkanen, Mika ; Korhonen, Matti</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c559t-df7f5e2467bd3afe7e6dc4da48133ee877e38050060ffd8a222b9b0a8029a1fe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Analysis</topic><topic>Cattle</topic><topic>Cell differentiation</topic><topic>Cells, Cultured</topic><topic>Collagen</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Infection</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Osteoblasts - cytology</topic><topic>Osteogenesis</topic><topic>Phosphatases</topic><topic>Physiological aspects</topic><topic>Primary Cell Culture - methods</topic><topic>Serum</topic><topic>Stem cells</topic><topic>Tissue engineering</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Castrén, Eeva</creatorcontrib><creatorcontrib>Sillat, Tarvo</creatorcontrib><creatorcontrib>Oja, Sofia</creatorcontrib><creatorcontrib>Noro, Ariel</creatorcontrib><creatorcontrib>Laitinen, Anita</creatorcontrib><creatorcontrib>Konttinen, Yrjö T</creatorcontrib><creatorcontrib>Lehenkari, Petri</creatorcontrib><creatorcontrib>Hukkanen, Mika</creatorcontrib><creatorcontrib>Korhonen, Matti</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical 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>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>Biological Science Database</collection><collection>Publicly Available Content 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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Stem cell research &amp; therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Castrén, Eeva</au><au>Sillat, Tarvo</au><au>Oja, Sofia</au><au>Noro, Ariel</au><au>Laitinen, Anita</au><au>Konttinen, Yrjö T</au><au>Lehenkari, Petri</au><au>Hukkanen, Mika</au><au>Korhonen, Matti</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Osteogenic differentiation of mesenchymal stromal cells in two-dimensional and three-dimensional cultures without animal serum</atitle><jtitle>Stem cell research &amp; therapy</jtitle><addtitle>Stem Cell Res Ther</addtitle><date>2015-09-07</date><risdate>2015</risdate><volume>6</volume><issue>1</issue><spage>167</spage><epage>167</epage><pages>167-167</pages><artnum>167</artnum><issn>1757-6512</issn><eissn>1757-6512</eissn><abstract>Bone marrow-derived mesenchymal stromal cells (MSCs) have been intensely studied for the purpose of developing solutions for clinical tissue engineering. Autologous MSCs can potentially be used to replace tissue defects, but the procedure also carries risks such as immunization and xenogeneic infection. Replacement of the commonly used fetal calf serum (FCS) with human platelet lysate and plasma (PLP) to support cell growth may reduce some of these risks. Altered media could, however, influence stem cell differentiation and we address this experimentally. We examined human MSC differentiation into the osteoblast lineage using in vitro two- and three-dimensional cultures with PLP or FCS as cell culture medium supplements. Differentiation was followed by quantitative polymerase chain reaction, and alkaline phosphatase activity, matrix formation and matrix calcium content were quantified. Three-dimensional culture, where human MSCs were grown on collagen sponges, markedly stimulated osteoblast differentiation; a fourfold increase in calcium deposition could be observed in both PLP and FCS groups. PLP-grown cells showed robust osteogenic differentiation both in two- and three-dimensional MSC cultures. The calcium content of the matrix in the two-dimensional PLP group at day 14 was 2.2-fold higher in comparison to the FCS group (p &lt; 0.0001), and at day 21 it was still 1.3-fold higher (p &lt; 0.001), suggesting earlier calcium accumulation to the matrix in the PLP group. This was supported by stronger Alizarin Red staining in the PLP group at day 14. In two-dimesional PLP cultures, cellular proliferation appeared to decrease during later stages of differentiation, while in the FCS group the number of cells increased throughout the experiment. In three-dimensional experiments, the PLP and FCS groups behaved more congruently, except for the alkaline phosphatase activity and mRNA levels which were markedly increased by PLP. Human PLP was at least equal to FCS in supporting osteogenic differentiation of human MSCs in two- and three-dimensional conditions; however, proliferation was inferior. As PLP is free of animal components, and thus represents reduced risk for xenogeneic infection, its use for human MSC-induced bone repair in the clinic by the three-dimensional live implants presented here appears a promising therapy option.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>26345992</pmid><doi>10.1186/s13287-015-0162-6</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1757-6512
ispartof Stem cell research & therapy, 2015-09, Vol.6 (1), p.167-167, Article 167
issn 1757-6512
1757-6512
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4562352
source MEDLINE; DOAJ Directory of Open Access Journals; PubMed Central Open Access; Springer Nature OA Free Journals; Springer Nature - Complete Springer Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central
subjects Adult
Analysis
Cattle
Cell differentiation
Cells, Cultured
Collagen
Genetic aspects
Health aspects
Humans
Infection
Mesenchymal Stromal Cells - cytology
Osteoblasts - cytology
Osteogenesis
Phosphatases
Physiological aspects
Primary Cell Culture - methods
Serum
Stem cells
Tissue engineering
title Osteogenic differentiation of mesenchymal stromal cells in two-dimensional and three-dimensional cultures without animal serum
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-21T18%3A18%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Osteogenic%20differentiation%20of%20mesenchymal%20stromal%20cells%20in%20two-dimensional%20and%20three-dimensional%20cultures%20without%20animal%20serum&rft.jtitle=Stem%20cell%20research%20&%20therapy&rft.au=Castr%C3%A9n,%20Eeva&rft.date=2015-09-07&rft.volume=6&rft.issue=1&rft.spage=167&rft.epage=167&rft.pages=167-167&rft.artnum=167&rft.issn=1757-6512&rft.eissn=1757-6512&rft_id=info:doi/10.1186/s13287-015-0162-6&rft_dat=%3Cgale_pubme%3EA541635125%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1772380870&rft_id=info:pmid/26345992&rft_galeid=A541635125&rfr_iscdi=true