Nanoparticle delivery of miR-223 to attenuate macrophage fusion
Abstract The foreign body response (FBR) begins with injury acquired during implantation of a biomaterial (BM) and is detrimental due to the eventual encapsulation of the implant. Fusion of macrophages to form foreign body giant cells (FBGC), a hallmark of the FBR, is the consequence of a multistep...
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| Veröffentlicht in: | Biomaterials 2016-05, Vol.89, p.127-135 |
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| creator | Moore, Laura Beth Sawyer, Andrew J Saucier-Sawyer, Jennifer Saltzman, W. Mark Kyriakides, Themis R |
| description | Abstract The foreign body response (FBR) begins with injury acquired during implantation of a biomaterial (BM) and is detrimental due to the eventual encapsulation of the implant. Fusion of macrophages to form foreign body giant cells (FBGC), a hallmark of the FBR, is the consequence of a multistep mechanism induced by interleukin (IL)-4 that includes the acquisition of a fusion competent state and subsequent cytoskeletal rearrangements. However, the precise mechanism, regulation, and interplay among molecular mediators to generate FBGCs are insufficiently understood. Seeking novel mediators of fusion that might be regulated at the post-transcriptional level, we examined the role of microRNAs (miRs) in this process. A miR microarray was screened and identified miR-223 as a negative regulator of macrophage fusion. In addition, transfection of primary macrophages with a mir-223 mimic attenuated IL-4-induced fusion. Furthermore, miR-223 KO mice and mir-223 deficient cells displayed increased fusion in vivo and in vitro, respectively. Finally, we developed a method for in vivo delivery of miR-223 mimic utilizing PLGA nanoparticles, which inhibited FBGC formation in a biomaterial implant model. Our results identify miR-223 as a negative regulator of fusion and demonstrate miR-223 mimic-loaded nanoparticles as a therapeutic inhibitor of macrophage fusion. |
| doi_str_mv | 10.1016/j.biomaterials.2016.02.036 |
| format | Article |
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Mark ; Kyriakides, Themis R</creator><creatorcontrib>Moore, Laura Beth ; Sawyer, Andrew J ; Saucier-Sawyer, Jennifer ; Saltzman, W. Mark ; Kyriakides, Themis R</creatorcontrib><description>Abstract The foreign body response (FBR) begins with injury acquired during implantation of a biomaterial (BM) and is detrimental due to the eventual encapsulation of the implant. Fusion of macrophages to form foreign body giant cells (FBGC), a hallmark of the FBR, is the consequence of a multistep mechanism induced by interleukin (IL)-4 that includes the acquisition of a fusion competent state and subsequent cytoskeletal rearrangements. However, the precise mechanism, regulation, and interplay among molecular mediators to generate FBGCs are insufficiently understood. Seeking novel mediators of fusion that might be regulated at the post-transcriptional level, we examined the role of microRNAs (miRs) in this process. A miR microarray was screened and identified miR-223 as a negative regulator of macrophage fusion. In addition, transfection of primary macrophages with a mir-223 mimic attenuated IL-4-induced fusion. Furthermore, miR-223 KO mice and mir-223 deficient cells displayed increased fusion in vivo and in vitro, respectively. Finally, we developed a method for in vivo delivery of miR-223 mimic utilizing PLGA nanoparticles, which inhibited FBGC formation in a biomaterial implant model. Our results identify miR-223 as a negative regulator of fusion and demonstrate miR-223 mimic-loaded nanoparticles as a therapeutic inhibitor of macrophage fusion.</description><identifier>ISSN: 0142-9612</identifier><identifier>EISSN: 1878-5905</identifier><identifier>DOI: 10.1016/j.biomaterials.2016.02.036</identifier><identifier>PMID: 26967647</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Advanced Basic Science ; Animals ; Attenuation ; biobased products ; Biomaterial ; Biomaterials ; Biomedical materials ; Cell Fusion ; Cells, Cultured ; cytoskeleton ; Dentistry ; encapsulation ; Foreign bodies ; Foreign body giant cell ; Gene Expression Regulation ; giant cells ; Giant Cells, Foreign-Body - cytology ; Giant Cells, Foreign-Body - metabolism ; interleukins ; Lactic Acid - chemistry ; Macrophage fusion ; Macrophages ; Macrophages - cytology ; Macrophages - metabolism ; Mice ; Mice, Knockout ; microarray technology ; microRNA ; MicroRNAs - administration & dosage ; MicroRNAs - genetics ; Nanoparticle ; Nanoparticles ; Nanoparticles - chemistry ; Polyglycolic Acid - chemistry ; Regulators ; Surgical implants ; therapeutics ; transfection</subject><ispartof>Biomaterials, 2016-05, Vol.89, p.127-135</ispartof><rights>Elsevier Ltd</rights><rights>2016 Elsevier Ltd</rights><rights>Copyright © 2016 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c641t-45f0a9b27249ddba452d38df01a434c239a44b52ab84d4681d9cb8ac3dfca59c3</citedby><cites>FETCH-LOGICAL-c641t-45f0a9b27249ddba452d38df01a434c239a44b52ab84d4681d9cb8ac3dfca59c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0142961216001587$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26967647$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moore, Laura Beth</creatorcontrib><creatorcontrib>Sawyer, Andrew J</creatorcontrib><creatorcontrib>Saucier-Sawyer, Jennifer</creatorcontrib><creatorcontrib>Saltzman, W. Mark</creatorcontrib><creatorcontrib>Kyriakides, Themis R</creatorcontrib><title>Nanoparticle delivery of miR-223 to attenuate macrophage fusion</title><title>Biomaterials</title><addtitle>Biomaterials</addtitle><description>Abstract The foreign body response (FBR) begins with injury acquired during implantation of a biomaterial (BM) and is detrimental due to the eventual encapsulation of the implant. Fusion of macrophages to form foreign body giant cells (FBGC), a hallmark of the FBR, is the consequence of a multistep mechanism induced by interleukin (IL)-4 that includes the acquisition of a fusion competent state and subsequent cytoskeletal rearrangements. However, the precise mechanism, regulation, and interplay among molecular mediators to generate FBGCs are insufficiently understood. Seeking novel mediators of fusion that might be regulated at the post-transcriptional level, we examined the role of microRNAs (miRs) in this process. A miR microarray was screened and identified miR-223 as a negative regulator of macrophage fusion. In addition, transfection of primary macrophages with a mir-223 mimic attenuated IL-4-induced fusion. Furthermore, miR-223 KO mice and mir-223 deficient cells displayed increased fusion in vivo and in vitro, respectively. Finally, we developed a method for in vivo delivery of miR-223 mimic utilizing PLGA nanoparticles, which inhibited FBGC formation in a biomaterial implant model. Our results identify miR-223 as a negative regulator of fusion and demonstrate miR-223 mimic-loaded nanoparticles as a therapeutic inhibitor of macrophage fusion.</description><subject>Advanced Basic Science</subject><subject>Animals</subject><subject>Attenuation</subject><subject>biobased products</subject><subject>Biomaterial</subject><subject>Biomaterials</subject><subject>Biomedical materials</subject><subject>Cell Fusion</subject><subject>Cells, Cultured</subject><subject>cytoskeleton</subject><subject>Dentistry</subject><subject>encapsulation</subject><subject>Foreign bodies</subject><subject>Foreign body giant cell</subject><subject>Gene Expression Regulation</subject><subject>giant cells</subject><subject>Giant Cells, Foreign-Body - cytology</subject><subject>Giant Cells, Foreign-Body - metabolism</subject><subject>interleukins</subject><subject>Lactic Acid - chemistry</subject><subject>Macrophage fusion</subject><subject>Macrophages</subject><subject>Macrophages - cytology</subject><subject>Macrophages - metabolism</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>microarray technology</subject><subject>microRNA</subject><subject>MicroRNAs - administration & dosage</subject><subject>MicroRNAs - genetics</subject><subject>Nanoparticle</subject><subject>Nanoparticles</subject><subject>Nanoparticles - chemistry</subject><subject>Polyglycolic Acid - chemistry</subject><subject>Regulators</subject><subject>Surgical implants</subject><subject>therapeutics</subject><subject>transfection</subject><issn>0142-9612</issn><issn>1878-5905</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkktv1DAUhSMEokPhL6CIFZsEvx8silB5ShVIPNaWY9-0HpJ4sJOR5t_jaEpV2LQry_Y559r3flX1AqMWIyxebdsuxNHOkIIdckvKWYtIi6h4UG2wkqrhGvGH1QZhRhotMDmpnuS8RWWPGHlcnRChhRRMbqo3X-wUdzbNwQ1QexjCHtKhjn09hm8NIbSeY23nGaalFKxH61LcXdlLqPslhzg9rR715RHw7Ho9rX5-eP_j_FNz8fXj5_O3F40TDM8N4z2yuiOSMO19ZxknnirfI2wZZY5QbRnrOLGdYp4Jhb12nbKO-t5Zrh09rc6OubulG8E7mOZkB7NLYbTpYKIN5t-bKVyZy7g3TBPGpCgBL68DUvy9QJ7NGLKDYbATxCUbUlpLGVFI3ynFCikkecm9WyoVJ5whru4hlZxKWcZSpK-P0tLsnBP0N__EyKwImK25jYBZETCImIJAMT-_3akb69-ZF8G7owDKvPYBkskuwOTAhwRuNj6G-9U5-y_GDWEKzg6_4AB5G5c0rR5scjGY7yuMK4tYFA65kvQPBGvduw</recordid><startdate>20160501</startdate><enddate>20160501</enddate><creator>Moore, Laura Beth</creator><creator>Sawyer, Andrew J</creator><creator>Saucier-Sawyer, Jennifer</creator><creator>Saltzman, W. Mark</creator><creator>Kyriakides, Themis R</creator><general>Elsevier Ltd</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>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>F28</scope><scope>JG9</scope><scope>L7M</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20160501</creationdate><title>Nanoparticle delivery of miR-223 to attenuate macrophage fusion</title><author>Moore, Laura Beth ; Sawyer, Andrew J ; Saucier-Sawyer, Jennifer ; Saltzman, W. Mark ; Kyriakides, Themis R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c641t-45f0a9b27249ddba452d38df01a434c239a44b52ab84d4681d9cb8ac3dfca59c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Advanced Basic Science</topic><topic>Animals</topic><topic>Attenuation</topic><topic>biobased products</topic><topic>Biomaterial</topic><topic>Biomaterials</topic><topic>Biomedical materials</topic><topic>Cell Fusion</topic><topic>Cells, Cultured</topic><topic>cytoskeleton</topic><topic>Dentistry</topic><topic>encapsulation</topic><topic>Foreign bodies</topic><topic>Foreign body giant cell</topic><topic>Gene Expression Regulation</topic><topic>giant cells</topic><topic>Giant Cells, Foreign-Body - cytology</topic><topic>Giant Cells, Foreign-Body - metabolism</topic><topic>interleukins</topic><topic>Lactic Acid - chemistry</topic><topic>Macrophage fusion</topic><topic>Macrophages</topic><topic>Macrophages - cytology</topic><topic>Macrophages - metabolism</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>microarray technology</topic><topic>microRNA</topic><topic>MicroRNAs - administration & dosage</topic><topic>MicroRNAs - genetics</topic><topic>Nanoparticle</topic><topic>Nanoparticles</topic><topic>Nanoparticles - chemistry</topic><topic>Polyglycolic Acid - chemistry</topic><topic>Regulators</topic><topic>Surgical implants</topic><topic>therapeutics</topic><topic>transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moore, Laura Beth</creatorcontrib><creatorcontrib>Sawyer, Andrew J</creatorcontrib><creatorcontrib>Saucier-Sawyer, Jennifer</creatorcontrib><creatorcontrib>Saltzman, W. Mark</creatorcontrib><creatorcontrib>Kyriakides, Themis R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</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><collection>Engineered Materials Abstracts</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biomaterials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moore, Laura Beth</au><au>Sawyer, Andrew J</au><au>Saucier-Sawyer, Jennifer</au><au>Saltzman, W. Mark</au><au>Kyriakides, Themis R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nanoparticle delivery of miR-223 to attenuate macrophage fusion</atitle><jtitle>Biomaterials</jtitle><addtitle>Biomaterials</addtitle><date>2016-05-01</date><risdate>2016</risdate><volume>89</volume><spage>127</spage><epage>135</epage><pages>127-135</pages><issn>0142-9612</issn><eissn>1878-5905</eissn><abstract>Abstract The foreign body response (FBR) begins with injury acquired during implantation of a biomaterial (BM) and is detrimental due to the eventual encapsulation of the implant. Fusion of macrophages to form foreign body giant cells (FBGC), a hallmark of the FBR, is the consequence of a multistep mechanism induced by interleukin (IL)-4 that includes the acquisition of a fusion competent state and subsequent cytoskeletal rearrangements. However, the precise mechanism, regulation, and interplay among molecular mediators to generate FBGCs are insufficiently understood. Seeking novel mediators of fusion that might be regulated at the post-transcriptional level, we examined the role of microRNAs (miRs) in this process. A miR microarray was screened and identified miR-223 as a negative regulator of macrophage fusion. In addition, transfection of primary macrophages with a mir-223 mimic attenuated IL-4-induced fusion. Furthermore, miR-223 KO mice and mir-223 deficient cells displayed increased fusion in vivo and in vitro, respectively. Finally, we developed a method for in vivo delivery of miR-223 mimic utilizing PLGA nanoparticles, which inhibited FBGC formation in a biomaterial implant model. Our results identify miR-223 as a negative regulator of fusion and demonstrate miR-223 mimic-loaded nanoparticles as a therapeutic inhibitor of macrophage fusion.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>26967647</pmid><doi>10.1016/j.biomaterials.2016.02.036</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Biomaterials, 2016-05, Vol.89, p.127-135 |
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| subjects | Advanced Basic Science Animals Attenuation biobased products Biomaterial Biomaterials Biomedical materials Cell Fusion Cells, Cultured cytoskeleton Dentistry encapsulation Foreign bodies Foreign body giant cell Gene Expression Regulation giant cells Giant Cells, Foreign-Body - cytology Giant Cells, Foreign-Body - metabolism interleukins Lactic Acid - chemistry Macrophage fusion Macrophages Macrophages - cytology Macrophages - metabolism Mice Mice, Knockout microarray technology microRNA MicroRNAs - administration & dosage MicroRNAs - genetics Nanoparticle Nanoparticles Nanoparticles - chemistry Polyglycolic Acid - chemistry Regulators Surgical implants therapeutics transfection |
| title | Nanoparticle delivery of miR-223 to attenuate macrophage fusion |
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