Extracellular Matrix Deposition in Engineered Micromass Cartilage Pellet Cultures: Measurements and Modelling
This article explores possible mechanisms governing extracellular matrix deposition in engineered cartilaginous cell pellets. A theoretical investigation is carried out alongside an experimental study measuring proteoglycan and collagen volume fractions within murine chondrogenic (ATDC-5) cell pelle...
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| Veröffentlicht in: | PloS one 2016-02, Vol.11 (2), p.e0147302-e0147302 |
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| creator | Lewis, Miranda C MacArthur, Ben D Tare, Rahul S Oreffo, Richard O C Please, Colin P |
| description | This article explores possible mechanisms governing extracellular matrix deposition in engineered cartilaginous cell pellets. A theoretical investigation is carried out alongside an experimental study measuring proteoglycan and collagen volume fractions within murine chondrogenic (ATDC-5) cell pellets. The simple mathematical model, which adopts a nutrient-dependent proteoglycan production rate, successfully reproduces the periphery-dominated proteoglycan deposition, characteristic of the growth pattern observed experimentally within pellets after 21 days of culture. The results suggest that this inhomogeneous proteoglycan production is due to nutrient deficiencies at the pellet centre. Our model analysis further indicates that a spatially uniform distribution of proteoglycan matrix could be maintained by initiating the culture process with a smaller-sized pellet. Finally, possible extensions are put forward with an aim to improve the model predictions for the early behaviour, where different mechanisms appear to dominate the matrix production within the pellets. |
| doi_str_mv | 10.1371/journal.pone.0147302 |
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A theoretical investigation is carried out alongside an experimental study measuring proteoglycan and collagen volume fractions within murine chondrogenic (ATDC-5) cell pellets. The simple mathematical model, which adopts a nutrient-dependent proteoglycan production rate, successfully reproduces the periphery-dominated proteoglycan deposition, characteristic of the growth pattern observed experimentally within pellets after 21 days of culture. The results suggest that this inhomogeneous proteoglycan production is due to nutrient deficiencies at the pellet centre. Our model analysis further indicates that a spatially uniform distribution of proteoglycan matrix could be maintained by initiating the culture process with a smaller-sized pellet. Finally, possible extensions are put forward with an aim to improve the model predictions for the early behaviour, where different mechanisms appear to dominate the matrix production within the pellets.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0147302</identifier><identifier>PMID: 26889833</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Animals ; Arthritis ; Biology and Life Sciences ; Cartilage ; Cartilage, Articular - cytology ; Cartilage, Articular - metabolism ; Cell culture ; Cell Culture Techniques ; Cell Differentiation ; Cell Line ; Chondrocytes - cytology ; Chondrocytes - metabolism ; Collagen ; Collagen - biosynthesis ; Deposition ; Extracellular matrix ; Extracellular Matrix - metabolism ; Growth factors ; Mathematical analysis ; Mathematical models ; Matrix methods ; Measurement ; Medicine and Health Sciences ; Mice ; Models, Statistical ; Nutrients ; Pellets ; Physical Sciences ; Polymers ; Proteoglycans ; Proteoglycans - biosynthesis ; Stem cells ; Studies ; Tissue engineering ; Tissue Engineering - methods ; Transplants & implants</subject><ispartof>PloS one, 2016-02, Vol.11 (2), p.e0147302-e0147302</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Lewis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Lewis et al 2016 Lewis et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-70bd0cd039869c9cdf51959c81752552680f6064e586c69c3440cac0fd5cabb13</citedby><cites>FETCH-LOGICAL-c692t-70bd0cd039869c9cdf51959c81752552680f6064e586c69c3440cac0fd5cabb13</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/PMC4758662/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758662/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23865,27923,27924,53790,53792,79371,79372</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26889833$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Nikitovic-Tzanakaki, Dragana</contributor><creatorcontrib>Lewis, Miranda C</creatorcontrib><creatorcontrib>MacArthur, Ben D</creatorcontrib><creatorcontrib>Tare, Rahul S</creatorcontrib><creatorcontrib>Oreffo, Richard O C</creatorcontrib><creatorcontrib>Please, Colin P</creatorcontrib><title>Extracellular Matrix Deposition in Engineered Micromass Cartilage Pellet Cultures: Measurements and Modelling</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>This article explores possible mechanisms governing extracellular matrix deposition in engineered cartilaginous cell pellets. A theoretical investigation is carried out alongside an experimental study measuring proteoglycan and collagen volume fractions within murine chondrogenic (ATDC-5) cell pellets. The simple mathematical model, which adopts a nutrient-dependent proteoglycan production rate, successfully reproduces the periphery-dominated proteoglycan deposition, characteristic of the growth pattern observed experimentally within pellets after 21 days of culture. The results suggest that this inhomogeneous proteoglycan production is due to nutrient deficiencies at the pellet centre. Our model analysis further indicates that a spatially uniform distribution of proteoglycan matrix could be maintained by initiating the culture process with a smaller-sized pellet. Finally, possible extensions are put forward with an aim to improve the model predictions for the early behaviour, where different mechanisms appear to dominate the matrix production within the pellets.</description><subject>Analysis</subject><subject>Animals</subject><subject>Arthritis</subject><subject>Biology and Life Sciences</subject><subject>Cartilage</subject><subject>Cartilage, Articular - cytology</subject><subject>Cartilage, Articular - metabolism</subject><subject>Cell culture</subject><subject>Cell Culture Techniques</subject><subject>Cell Differentiation</subject><subject>Cell Line</subject><subject>Chondrocytes - cytology</subject><subject>Chondrocytes - metabolism</subject><subject>Collagen</subject><subject>Collagen - biosynthesis</subject><subject>Deposition</subject><subject>Extracellular matrix</subject><subject>Extracellular Matrix - metabolism</subject><subject>Growth factors</subject><subject>Mathematical analysis</subject><subject>Mathematical models</subject><subject>Matrix methods</subject><subject>Measurement</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Models, Statistical</subject><subject>Nutrients</subject><subject>Pellets</subject><subject>Physical Sciences</subject><subject>Polymers</subject><subject>Proteoglycans</subject><subject>Proteoglycans - biosynthesis</subject><subject>Stem cells</subject><subject>Studies</subject><subject>Tissue engineering</subject><subject>Tissue Engineering - methods</subject><subject>Transplants & implants</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</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><sourceid>DOA</sourceid><recordid>eNqNk02P0zAQhiMEYpeFf4AgEhKCQ4sdJ3bCAWlVClTaahFfV8txJqkrxy62g8q_x6HZVYv2gHKIZT_vOx7PTJI8xWiOCcNvtnZwRuj5zhqYI5wzgrJ7yTmuSDajGSL3j9ZnySPvtwgVpKT0YXKW0bKsSkLOk365D05I0HrQwqVrEZzap-9hZ70KyppUmXRpOmUAHDTpWklne-F9uhAuKC06SD9HMYR0MegwOPBv0zUIH1c9mOBTYaLKNpFRpnucPGiF9vBk-l8k3z8svy0-za6uP64Wl1czSasszBiqGyQbRKqSVrKSTVvgqqhkiVmRFUW8PWopojkUJY0KSfIcSSFR2xRS1DUmF8nzg-9OW8-nl_IcM4YzhjFlkVgdiMaKLd851Qv3m1uh-N8N6zo-Jig1cJpJiOFZWcgyZ4iJDMqsLaAktG5qmUWvd1O0oe6hkTFvJ_SJ6emJURve2V88ZzEBOhq8mgyc_TmAD7xXfqyJMGCH8d40xi1yVkX0xT_o3dlNVCdiAsq0dizyaMov85xQnNOcRmp-BxW_BnolY1u1Ku6fCF6fCCITYB86MXjPV1-__D97_eOUfXnEbkDosPFWD2MD-lMwP4CxC7130N4-MkZ8nIqb1-DjVPBpKqLs2XGBbkU3Y0D-AHWTB8c</recordid><startdate>20160218</startdate><enddate>20160218</enddate><creator>Lewis, Miranda C</creator><creator>MacArthur, Ben D</creator><creator>Tare, Rahul S</creator><creator>Oreffo, Richard O C</creator><creator>Please, Colin P</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160218</creationdate><title>Extracellular Matrix Deposition in Engineered Micromass Cartilage Pellet Cultures: Measurements and Modelling</title><author>Lewis, Miranda C ; MacArthur, Ben D ; Tare, Rahul S ; Oreffo, Richard O C ; Please, Colin P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-70bd0cd039869c9cdf51959c81752552680f6064e586c69c3440cac0fd5cabb13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Analysis</topic><topic>Animals</topic><topic>Arthritis</topic><topic>Biology and Life Sciences</topic><topic>Cartilage</topic><topic>Cartilage, Articular - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lewis, Miranda C</au><au>MacArthur, Ben D</au><au>Tare, Rahul S</au><au>Oreffo, Richard O C</au><au>Please, Colin P</au><au>Nikitovic-Tzanakaki, Dragana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Extracellular Matrix Deposition in Engineered Micromass Cartilage Pellet Cultures: Measurements and Modelling</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-02-18</date><risdate>2016</risdate><volume>11</volume><issue>2</issue><spage>e0147302</spage><epage>e0147302</epage><pages>e0147302-e0147302</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>This article explores possible mechanisms governing extracellular matrix deposition in engineered cartilaginous cell pellets. A theoretical investigation is carried out alongside an experimental study measuring proteoglycan and collagen volume fractions within murine chondrogenic (ATDC-5) cell pellets. The simple mathematical model, which adopts a nutrient-dependent proteoglycan production rate, successfully reproduces the periphery-dominated proteoglycan deposition, characteristic of the growth pattern observed experimentally within pellets after 21 days of culture. The results suggest that this inhomogeneous proteoglycan production is due to nutrient deficiencies at the pellet centre. Our model analysis further indicates that a spatially uniform distribution of proteoglycan matrix could be maintained by initiating the culture process with a smaller-sized pellet. Finally, possible extensions are put forward with an aim to improve the model predictions for the early behaviour, where different mechanisms appear to dominate the matrix production within the pellets.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26889833</pmid><doi>10.1371/journal.pone.0147302</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Analysis Animals Arthritis Biology and Life Sciences Cartilage Cartilage, Articular - cytology Cartilage, Articular - metabolism Cell culture Cell Culture Techniques Cell Differentiation Cell Line Chondrocytes - cytology Chondrocytes - metabolism Collagen Collagen - biosynthesis Deposition Extracellular matrix Extracellular Matrix - metabolism Growth factors Mathematical analysis Mathematical models Matrix methods Measurement Medicine and Health Sciences Mice Models, Statistical Nutrients Pellets Physical Sciences Polymers Proteoglycans Proteoglycans - biosynthesis Stem cells Studies Tissue engineering Tissue Engineering - methods Transplants & implants |
| title | Extracellular Matrix Deposition in Engineered Micromass Cartilage Pellet Cultures: Measurements and Modelling |
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