Optimizing combination of vascular endothelial growth factor and mesenchymal stem cells on ectopic bone formation in SCID mice
Introduction: Insufficient blood supply may limit bone regeneration in bone defects. Vascular endothelial growth factor (VEGF) promotes angiogenesis by increasing endothelial migration. This outcome, however, could depend on time of application. Sheep mesenchymal stem cells (MSCs) in severe combined...
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| Veröffentlicht in: | Journal of biomedical materials research. Part A 2017-12, Vol.105 (12), p.3326-3332 |
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| creator | Dreyer, Chris H. Kjærgaard, Kristian Ditzel, Nicholas Jørgensen, Niklas R. Overgaard, Søren Ding, Ming |
| description | Introduction: Insufficient blood supply may limit bone regeneration in bone defects. Vascular endothelial growth factor (VEGF) promotes angiogenesis by increasing endothelial migration. This outcome, however, could depend on time of application. Sheep mesenchymal stem cells (MSCs) in severe combined immunodeficient (SCID) mice were used in this study to evaluate optimal time points for VEGF stimulation to increase bone formation. Methods: Twenty‐eight SCID (NOD.CB17‐Prkdcscid/J) mice had hydroxyapatite granules seeded with 5 × 105 MSCs inserted subcutaneous. Pellets released VEGF on days 1–7, days 1–14, days 1–21, days 1–42, days 7–14, and days 21–42. After 8 weeks, the implant‐bone‐blocks were harvested, paraffin embedded, sectioned, and stained with both hematoxylin and eosin (HE) and immunohistochemistry for human vimentin (hVim) staining. Blood samples were collected for determination of bone‐related biomarkers in serum. Results: The groups with 5 × 105 MSCs and VEGF stimulation on days 1–14 and days 1–21 showed more bone formation when compared to the control group of 5 × 105 MSCs alone (p |
| doi_str_mv | 10.1002/jbm.a.36195 |
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Vascular endothelial growth factor (VEGF) promotes angiogenesis by increasing endothelial migration. This outcome, however, could depend on time of application. Sheep mesenchymal stem cells (MSCs) in severe combined immunodeficient (SCID) mice were used in this study to evaluate optimal time points for VEGF stimulation to increase bone formation. Methods: Twenty‐eight SCID (NOD.CB17‐Prkdcscid/J) mice had hydroxyapatite granules seeded with 5 × 105 MSCs inserted subcutaneous. Pellets released VEGF on days 1–7, days 1–14, days 1–21, days 1–42, days 7–14, and days 21–42. After 8 weeks, the implant‐bone‐blocks were harvested, paraffin embedded, sectioned, and stained with both hematoxylin and eosin (HE) and immunohistochemistry for human vimentin (hVim) staining. Blood samples were collected for determination of bone‐related biomarkers in serum. Results: The groups with 5 × 105 MSCs and VEGF stimulation on days 1–14 and days 1–21 showed more bone formation when compared to the control group of 5 × 105 MSCs alone (p < 0.01). Serum biomarkers had no significant values. The hVim staining confirmed the ovine origin of the observed ectopic bone formation. Conclusion: Optimal bone formation of MSCs was reached when stimulating with VEGF during the first 14 or 21 days after surgery. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3326–3332, 2017.</description><identifier>ISSN: 1549-3296</identifier><identifier>EISSN: 1552-4965</identifier><identifier>DOI: 10.1002/jbm.a.36195</identifier><identifier>PMID: 28879669</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Angiogenesis ; Animals ; Biomarkers ; Biomarkers - blood ; Biomedical materials ; Blood ; bone formation ; Bone growth ; Bone implants ; Cells, Cultured ; Durapatite - chemistry ; Female ; Humans ; Hydroxyapatite ; Immunodeficiency ; Immunohistochemistry ; Mesenchymal Stem Cell Transplantation - methods ; Mesenchymal stem cells ; Mesenchymal Stromal Cells - cytology ; Mesenchyme ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Optimization ; Ossification (ectopic) ; Osteogenesis ; Osteogenesis - drug effects ; Paraffin ; Regeneration ; Regeneration (physiology) ; severe combined immunodeficient mice ; Sheep ; Staining ; Stem cell transplantation ; Stem cells ; Stimulation ; Surgery ; Surgical implants ; tissue engineering ; Tissue Engineering - methods ; Tissue Scaffolds - chemistry ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - administration & dosage ; Vascular Endothelial Growth Factor A - therapeutic use ; Vimentin</subject><ispartof>Journal of biomedical materials research. 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Part A</title><addtitle>J Biomed Mater Res A</addtitle><description>Introduction: Insufficient blood supply may limit bone regeneration in bone defects. Vascular endothelial growth factor (VEGF) promotes angiogenesis by increasing endothelial migration. This outcome, however, could depend on time of application. Sheep mesenchymal stem cells (MSCs) in severe combined immunodeficient (SCID) mice were used in this study to evaluate optimal time points for VEGF stimulation to increase bone formation. Methods: Twenty‐eight SCID (NOD.CB17‐Prkdcscid/J) mice had hydroxyapatite granules seeded with 5 × 105 MSCs inserted subcutaneous. Pellets released VEGF on days 1–7, days 1–14, days 1–21, days 1–42, days 7–14, and days 21–42. After 8 weeks, the implant‐bone‐blocks were harvested, paraffin embedded, sectioned, and stained with both hematoxylin and eosin (HE) and immunohistochemistry for human vimentin (hVim) staining. Blood samples were collected for determination of bone‐related biomarkers in serum. Results: The groups with 5 × 105 MSCs and VEGF stimulation on days 1–14 and days 1–21 showed more bone formation when compared to the control group of 5 × 105 MSCs alone (p < 0.01). Serum biomarkers had no significant values. The hVim staining confirmed the ovine origin of the observed ectopic bone formation. Conclusion: Optimal bone formation of MSCs was reached when stimulating with VEGF during the first 14 or 21 days after surgery. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3326–3332, 2017.</description><subject>Angiogenesis</subject><subject>Animals</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Biomedical materials</subject><subject>Blood</subject><subject>bone formation</subject><subject>Bone growth</subject><subject>Bone implants</subject><subject>Cells, Cultured</subject><subject>Durapatite - chemistry</subject><subject>Female</subject><subject>Humans</subject><subject>Hydroxyapatite</subject><subject>Immunodeficiency</subject><subject>Immunohistochemistry</subject><subject>Mesenchymal Stem Cell Transplantation - methods</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Mesenchyme</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>Optimization</subject><subject>Ossification (ectopic)</subject><subject>Osteogenesis</subject><subject>Osteogenesis - drug effects</subject><subject>Paraffin</subject><subject>Regeneration</subject><subject>Regeneration (physiology)</subject><subject>severe combined immunodeficient mice</subject><subject>Sheep</subject><subject>Staining</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Stimulation</subject><subject>Surgery</subject><subject>Surgical implants</subject><subject>tissue engineering</subject><subject>Tissue Engineering - methods</subject><subject>Tissue Scaffolds - chemistry</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A - administration & dosage</subject><subject>Vascular Endothelial Growth Factor A - therapeutic use</subject><subject>Vimentin</subject><issn>1549-3296</issn><issn>1552-4965</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90bFP3DAUBnALtQJKmdgrS10qVTnsJHbikV4LBYEYCrNlOy-cT7F9tZOiY-jfXh-hHTowvSe9nz496UPohJIFJaQ8XWu3UIuKU8H20CFlrCxqwdmb3V6LoioFP0DvUlpnzAkr99FB2baN4Fwcot-3m9E6-2T9AzbBaevVaIPHoce_VDLToCIG34VxBYNVA36I4XFc4V6ZMUSsfIcdJPBmtXX5mkZw2MAwJJwzIJuNNVgHD7gP0c3R1uMfy8uv2FkD79HbXg0Jjl_mEbo__3a3_F5c315cLs-uC1OJhhV1TbThrW4FVS3UlJhGEKGU6TTptNBcNNBqzuoG-q4ERiswFeH5oIkxNVRH6NOcu4nh5wRplM6m3aPKQ5iSpKLivCQN5Zl-_I-uwxR9_i4rxkndsqbJ6vOsTAwpRejlJlqn4lZSIne1yFyLVPK5lqw_vGRO2kH3z_7tIYNyBo92gO1rWfLqy83ZnPoHF7yaAw</recordid><startdate>201712</startdate><enddate>201712</enddate><creator>Dreyer, Chris H.</creator><creator>Kjærgaard, Kristian</creator><creator>Ditzel, Nicholas</creator><creator>Jørgensen, Niklas R.</creator><creator>Overgaard, Søren</creator><creator>Ding, Ming</creator><general>Wiley Subscription Services, 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>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</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/0000-0002-3762-0559</orcidid></search><sort><creationdate>201712</creationdate><title>Optimizing combination of vascular endothelial growth factor and mesenchymal stem cells on ectopic bone formation in SCID mice</title><author>Dreyer, Chris H. ; Kjærgaard, Kristian ; Ditzel, Nicholas ; Jørgensen, Niklas R. ; Overgaard, Søren ; Ding, Ming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3975-440bc68b891a8e410c7909aacdb0db9b697e8b6547efd2e513ec3069b6b0cc4e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Angiogenesis</topic><topic>Animals</topic><topic>Biomarkers</topic><topic>Biomarkers - blood</topic><topic>Biomedical materials</topic><topic>Blood</topic><topic>bone formation</topic><topic>Bone growth</topic><topic>Bone implants</topic><topic>Cells, Cultured</topic><topic>Durapatite - chemistry</topic><topic>Female</topic><topic>Humans</topic><topic>Hydroxyapatite</topic><topic>Immunodeficiency</topic><topic>Immunohistochemistry</topic><topic>Mesenchymal Stem Cell Transplantation - methods</topic><topic>Mesenchymal stem cells</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Mesenchyme</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Mice, SCID</topic><topic>Optimization</topic><topic>Ossification (ectopic)</topic><topic>Osteogenesis</topic><topic>Osteogenesis - drug effects</topic><topic>Paraffin</topic><topic>Regeneration</topic><topic>Regeneration (physiology)</topic><topic>severe combined immunodeficient mice</topic><topic>Sheep</topic><topic>Staining</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Stimulation</topic><topic>Surgery</topic><topic>Surgical implants</topic><topic>tissue engineering</topic><topic>Tissue Engineering - methods</topic><topic>Tissue Scaffolds - chemistry</topic><topic>Vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A - administration & dosage</topic><topic>Vascular Endothelial Growth Factor A - therapeutic use</topic><topic>Vimentin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dreyer, Chris H.</creatorcontrib><creatorcontrib>Kjærgaard, Kristian</creatorcontrib><creatorcontrib>Ditzel, Nicholas</creatorcontrib><creatorcontrib>Jørgensen, Niklas R.</creatorcontrib><creatorcontrib>Overgaard, Søren</creatorcontrib><creatorcontrib>Ding, Ming</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of biomedical materials research. Part A</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dreyer, Chris H.</au><au>Kjærgaard, Kristian</au><au>Ditzel, Nicholas</au><au>Jørgensen, Niklas R.</au><au>Overgaard, Søren</au><au>Ding, Ming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Optimizing combination of vascular endothelial growth factor and mesenchymal stem cells on ectopic bone formation in SCID mice</atitle><jtitle>Journal of biomedical materials research. Part A</jtitle><addtitle>J Biomed Mater Res A</addtitle><date>2017-12</date><risdate>2017</risdate><volume>105</volume><issue>12</issue><spage>3326</spage><epage>3332</epage><pages>3326-3332</pages><issn>1549-3296</issn><eissn>1552-4965</eissn><abstract>Introduction: Insufficient blood supply may limit bone regeneration in bone defects. Vascular endothelial growth factor (VEGF) promotes angiogenesis by increasing endothelial migration. This outcome, however, could depend on time of application. Sheep mesenchymal stem cells (MSCs) in severe combined immunodeficient (SCID) mice were used in this study to evaluate optimal time points for VEGF stimulation to increase bone formation. Methods: Twenty‐eight SCID (NOD.CB17‐Prkdcscid/J) mice had hydroxyapatite granules seeded with 5 × 105 MSCs inserted subcutaneous. Pellets released VEGF on days 1–7, days 1–14, days 1–21, days 1–42, days 7–14, and days 21–42. After 8 weeks, the implant‐bone‐blocks were harvested, paraffin embedded, sectioned, and stained with both hematoxylin and eosin (HE) and immunohistochemistry for human vimentin (hVim) staining. Blood samples were collected for determination of bone‐related biomarkers in serum. Results: The groups with 5 × 105 MSCs and VEGF stimulation on days 1–14 and days 1–21 showed more bone formation when compared to the control group of 5 × 105 MSCs alone (p < 0.01). Serum biomarkers had no significant values. The hVim staining confirmed the ovine origin of the observed ectopic bone formation. Conclusion: Optimal bone formation of MSCs was reached when stimulating with VEGF during the first 14 or 21 days after surgery. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3326–3332, 2017.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28879669</pmid><doi>10.1002/jbm.a.36195</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-3762-0559</orcidid></addata></record> |
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| subjects | Angiogenesis Animals Biomarkers Biomarkers - blood Biomedical materials Blood bone formation Bone growth Bone implants Cells, Cultured Durapatite - chemistry Female Humans Hydroxyapatite Immunodeficiency Immunohistochemistry Mesenchymal Stem Cell Transplantation - methods Mesenchymal stem cells Mesenchymal Stromal Cells - cytology Mesenchyme Mice Mice, Inbred NOD Mice, SCID Optimization Ossification (ectopic) Osteogenesis Osteogenesis - drug effects Paraffin Regeneration Regeneration (physiology) severe combined immunodeficient mice Sheep Staining Stem cell transplantation Stem cells Stimulation Surgery Surgical implants tissue engineering Tissue Engineering - methods Tissue Scaffolds - chemistry Vascular endothelial growth factor Vascular Endothelial Growth Factor A - administration & dosage Vascular Endothelial Growth Factor A - therapeutic use Vimentin |
| title | Optimizing combination of vascular endothelial growth factor and mesenchymal stem cells on ectopic bone formation in SCID mice |
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