Engineering functional BMP-2 expressing teratoma-derived fibroblasts for enhancing osteogenesis
Bone morphogenetic protein 2 (BMP-2) is considered an effective growth factor for bone formation, and is used for making osteo-inductive scaffolds, but the related clinical investigations have shown low success rates. In this study, we genetically manipulated teratoma-derived fibroblast (TDF) cells...
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| Veröffentlicht in: | Scientific reports 2018-10, Vol.8 (1), p.14581-10, Article 14581 |
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| description | Bone morphogenetic protein 2 (BMP-2) is considered an effective growth factor for bone formation, and is used for making osteo-inductive scaffolds, but the related clinical investigations have shown low success rates. In this study, we genetically manipulated teratoma-derived fibroblast (TDF) cells by simultaneous introduction of
BMP-2
and
herpes simplex virus-thymidine kinase (HSV-tk)
encoding genes. Self-production of BMP-2 in TDF cells strongly enhanced the alkaline phosphatase (ALP) activity, calcium content, and elevated the mRNA expression of osteogenic marker genes during
in vitro
osteogenesis. The bone formation volume was also remarkably enhanced in calvarial and femoral critical-size defect models. Ganciclovir (GCV) treatment induced apoptosis in TDF cells co-expressing HSV-tk and BMP-2, implying that HSV-tk suicide gene can modulate the side-effects of stem cell therapy, e.g., development of uncontrollable teratoma and tumor formation. Altogether, our findings revealed a safe and highly efficient technique with potential therapeutic applications for bone regeneration. |
| doi_str_mv | 10.1038/s41598-018-32946-6 |
| format | Article |
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BMP-2
and
herpes simplex virus-thymidine kinase (HSV-tk)
encoding genes. Self-production of BMP-2 in TDF cells strongly enhanced the alkaline phosphatase (ALP) activity, calcium content, and elevated the mRNA expression of osteogenic marker genes during
in vitro
osteogenesis. The bone formation volume was also remarkably enhanced in calvarial and femoral critical-size defect models. Ganciclovir (GCV) treatment induced apoptosis in TDF cells co-expressing HSV-tk and BMP-2, implying that HSV-tk suicide gene can modulate the side-effects of stem cell therapy, e.g., development of uncontrollable teratoma and tumor formation. Altogether, our findings revealed a safe and highly efficient technique with potential therapeutic applications for bone regeneration.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-018-32946-6</identifier><identifier>PMID: 30275449</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 13/100 ; 13/107 ; 13/51 ; 14 ; 14/19 ; 14/63 ; 38 ; 38/77 ; 42/109 ; 631/1647/1511 ; 692/308/1426 ; Alkaline phosphatase ; Apoptosis ; Bone growth ; Bone morphogenetic protein 2 ; Calcium ; Femur ; Fibroblasts ; Ganciclovir ; Gene expression ; Genetic engineering ; Herpes simplex ; Humanities and Social Sciences ; multidisciplinary ; Osteogenesis ; Regeneration ; Science ; Science (multidisciplinary) ; Stem cells ; Suicide ; Suicide genes ; Teratoma ; Therapeutic applications ; Thymidine ; Thymidine kinase</subject><ispartof>Scientific reports, 2018-10, Vol.8 (1), p.14581-10, Article 14581</ispartof><rights>The Author(s) 2018</rights><rights>2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c511t-d7630ae46861f43d80dae8a8b2bcfdaf543ea6be1d2e0ddf537c8b9307fd9a8e3</citedby><cites>FETCH-LOGICAL-c511t-d7630ae46861f43d80dae8a8b2bcfdaf543ea6be1d2e0ddf537c8b9307fd9a8e3</cites><orcidid>0000-0002-8488-9091</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167319/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167319/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27923,27924,41119,42188,51575,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30275449$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Go, Yoon Young</creatorcontrib><creatorcontrib>Mun, Ji Yeon</creatorcontrib><creatorcontrib>Chae, Sung-Won</creatorcontrib><creatorcontrib>Kim, Shin Hye</creatorcontrib><creatorcontrib>Song, Hoseok</creatorcontrib><creatorcontrib>Song, Jae-Jun</creatorcontrib><title>Engineering functional BMP-2 expressing teratoma-derived fibroblasts for enhancing osteogenesis</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Bone morphogenetic protein 2 (BMP-2) is considered an effective growth factor for bone formation, and is used for making osteo-inductive scaffolds, but the related clinical investigations have shown low success rates. In this study, we genetically manipulated teratoma-derived fibroblast (TDF) cells by simultaneous introduction of
BMP-2
and
herpes simplex virus-thymidine kinase (HSV-tk)
encoding genes. Self-production of BMP-2 in TDF cells strongly enhanced the alkaline phosphatase (ALP) activity, calcium content, and elevated the mRNA expression of osteogenic marker genes during
in vitro
osteogenesis. The bone formation volume was also remarkably enhanced in calvarial and femoral critical-size defect models. Ganciclovir (GCV) treatment induced apoptosis in TDF cells co-expressing HSV-tk and BMP-2, implying that HSV-tk suicide gene can modulate the side-effects of stem cell therapy, e.g., development of uncontrollable teratoma and tumor formation. Altogether, our findings revealed a safe and highly efficient technique with potential therapeutic applications for bone regeneration.</description><subject>13</subject><subject>13/100</subject><subject>13/107</subject><subject>13/51</subject><subject>14</subject><subject>14/19</subject><subject>14/63</subject><subject>38</subject><subject>38/77</subject><subject>42/109</subject><subject>631/1647/1511</subject><subject>692/308/1426</subject><subject>Alkaline phosphatase</subject><subject>Apoptosis</subject><subject>Bone growth</subject><subject>Bone morphogenetic protein 2</subject><subject>Calcium</subject><subject>Femur</subject><subject>Fibroblasts</subject><subject>Ganciclovir</subject><subject>Gene expression</subject><subject>Genetic engineering</subject><subject>Herpes simplex</subject><subject>Humanities and Social Sciences</subject><subject>multidisciplinary</subject><subject>Osteogenesis</subject><subject>Regeneration</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Stem cells</subject><subject>Suicide</subject><subject>Suicide genes</subject><subject>Teratoma</subject><subject>Therapeutic applications</subject><subject>Thymidine</subject><subject>Thymidine kinase</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kU1vFSEUhonR2Kb2D7gwk7hxg_IxMMzGRJv6kdToQteEGQ63NHPhyplp6r-XcWqtLmQDyXnOe4CHkKecveRMmlfYctUbyrihUvStpvoBORasVVRIIR7eOx-RU8QrVpeqIO8fkyPJRKfatj8m9jztYgIoMe2asKRxjjm5qXn76QsVDdwcCiCutRmKm_PeUV_Za_BNiEPJw-Rwxibk0kC6dGlc0Ywz5B0kwIhPyKPgJoTT2_2EfHt3_vXsA734_P7j2ZsLOirOZ-o7LZmDVhvNQyu9Yd6BcWYQwxi8C6qV4PQA3Atg3gclu9EMvWRd8L0zIE_I6y33sAx78COkubjJHkrcu_LDZhft35UUL-0uX1vNdSd5XwNe3AaU_H0BnO0-4gjT5BLkBa3gXHWKac0r-vwf9Covpf7aRgkpNdOVEhs1loxYINxdhjO7KrSbQlsV2l8K7dr07P4z7lp-C6uA3AA8rMqg_Jn9n9ifpLip0w</recordid><startdate>20181001</startdate><enddate>20181001</enddate><creator>Go, Yoon Young</creator><creator>Mun, Ji Yeon</creator><creator>Chae, Sung-Won</creator><creator>Kim, Shin Hye</creator><creator>Song, Hoseok</creator><creator>Song, Jae-Jun</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</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>AEUYN</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>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8488-9091</orcidid></search><sort><creationdate>20181001</creationdate><title>Engineering functional BMP-2 expressing teratoma-derived fibroblasts for enhancing osteogenesis</title><author>Go, Yoon Young ; 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In this study, we genetically manipulated teratoma-derived fibroblast (TDF) cells by simultaneous introduction of
BMP-2
and
herpes simplex virus-thymidine kinase (HSV-tk)
encoding genes. Self-production of BMP-2 in TDF cells strongly enhanced the alkaline phosphatase (ALP) activity, calcium content, and elevated the mRNA expression of osteogenic marker genes during
in vitro
osteogenesis. The bone formation volume was also remarkably enhanced in calvarial and femoral critical-size defect models. Ganciclovir (GCV) treatment induced apoptosis in TDF cells co-expressing HSV-tk and BMP-2, implying that HSV-tk suicide gene can modulate the side-effects of stem cell therapy, e.g., development of uncontrollable teratoma and tumor formation. Altogether, our findings revealed a safe and highly efficient technique with potential therapeutic applications for bone regeneration.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30275449</pmid><doi>10.1038/s41598-018-32946-6</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-8488-9091</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 13 13/100 13/107 13/51 14 14/19 14/63 38 38/77 42/109 631/1647/1511 692/308/1426 Alkaline phosphatase Apoptosis Bone growth Bone morphogenetic protein 2 Calcium Femur Fibroblasts Ganciclovir Gene expression Genetic engineering Herpes simplex Humanities and Social Sciences multidisciplinary Osteogenesis Regeneration Science Science (multidisciplinary) Stem cells Suicide Suicide genes Teratoma Therapeutic applications Thymidine Thymidine kinase |
| title | Engineering functional BMP-2 expressing teratoma-derived fibroblasts for enhancing osteogenesis |
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