Allogeneic Mesenchymal Stem Cell Therapy for Bisphosphonate-Related Jaw Osteonecrosis in Swine
Bisphosphonates (BPs), which are used to treat a variety of clinical disorders, have the side effect of jawbone necrosis. Currently, there is no reliable treatment for BP-related osteonecrosis of the jaw (BRONJ) due to a lack of understanding of its pathogenesis. To investigate the pathogenesis of B...
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| Veröffentlicht in: | Stem cells and development 2013-07, Vol.22 (14), p.247-2056 |
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| creator | Li, Yunsheng Xu, Junji Mao, Lisha Liu, Yi Gao, Runtao Zheng, Zongmei Chen, Wanjun Le, Anh Shi, Songtao Wang, Songlin |
| description | Bisphosphonates (BPs), which are used to treat a variety of clinical disorders, have the side effect of jawbone necrosis. Currently, there is no reliable treatment for BP-related osteonecrosis of the jaw (BRONJ) due to a lack of understanding of its pathogenesis. To investigate the pathogenesis of BRONJ and observe the treatment effect of bone marrow mesenchymal stem cell (BMMSC) transplantation, we established a preclinical animal model of BRONJ in miniature pigs (minipigs). After treatment with zoledronic acid, the clinical and radiographic manifestations of BRONJ could be observed in minipigs after first premolar extraction. The biological and immunological properties of BMMSCs were impaired in the BP-treated minipigs. Moreover, the ratio of Foxp3-positive regulatory T-cells (Tregs) in peripheral blood decreased, and interleukin (IL)-17 increased in the serum of BP-treated minipigs. After allogeneic BMMSC transplantation via intravenous infusion, mucosal healing and bone reconstruction were observed; IL-17 levels were reduced; and Tregs were elevated. In summary, we established a clinically relevant BRONJ model in minipigs and tested a promising allogeneic BMMSC-based therapy, which may have potential clinical applications for treating BRONJ. |
| doi_str_mv | 10.1089/scd.2012.0615 |
| format | Article |
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Currently, there is no reliable treatment for BP-related osteonecrosis of the jaw (BRONJ) due to a lack of understanding of its pathogenesis. To investigate the pathogenesis of BRONJ and observe the treatment effect of bone marrow mesenchymal stem cell (BMMSC) transplantation, we established a preclinical animal model of BRONJ in miniature pigs (minipigs). After treatment with zoledronic acid, the clinical and radiographic manifestations of BRONJ could be observed in minipigs after first premolar extraction. The biological and immunological properties of BMMSCs were impaired in the BP-treated minipigs. Moreover, the ratio of Foxp3-positive regulatory T-cells (Tregs) in peripheral blood decreased, and interleukin (IL)-17 increased in the serum of BP-treated minipigs. After allogeneic BMMSC transplantation via intravenous infusion, mucosal healing and bone reconstruction were observed; IL-17 levels were reduced; and Tregs were elevated. In summary, we established a clinically relevant BRONJ model in minipigs and tested a promising allogeneic BMMSC-based therapy, which may have potential clinical applications for treating BRONJ.</description><identifier>ISSN: 1547-3287</identifier><identifier>EISSN: 1557-8534</identifier><identifier>DOI: 10.1089/scd.2012.0615</identifier><identifier>PMID: 23461552</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Animals ; Biomarkers - metabolism ; Bisphosphonate-Associated Osteonecrosis of the Jaw - diagnostic imaging ; Bisphosphonate-Associated Osteonecrosis of the Jaw - pathology ; Bisphosphonate-Associated Osteonecrosis of the Jaw - therapy ; Diphosphonates ; Disease Models, Animal ; Female ; Forkhead Transcription Factors - metabolism ; Humans ; Imidazoles ; Interleukin-17 - blood ; Male ; Mandible - diagnostic imaging ; Mandible - pathology ; Mesenchymal Stem Cell Transplantation ; Original Research Reports ; Radiography ; Swine ; Swine, Miniature ; T-Lymphocytes, Regulatory - pathology ; Transplantation, Homologous</subject><ispartof>Stem cells and development, 2013-07, Vol.22 (14), p.247-2056</ispartof><rights>2013, Mary Ann Liebert, Inc.</rights><rights>Copyright 2013, Mary Ann Liebert, Inc. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c431t-17da997aa87e049d5da67a03cc846eff46b5c8771e1d96673085f620b423edb73</citedby><cites>FETCH-LOGICAL-c431t-17da997aa87e049d5da67a03cc846eff46b5c8771e1d96673085f620b423edb73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23461552$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Yunsheng</creatorcontrib><creatorcontrib>Xu, Junji</creatorcontrib><creatorcontrib>Mao, Lisha</creatorcontrib><creatorcontrib>Liu, Yi</creatorcontrib><creatorcontrib>Gao, Runtao</creatorcontrib><creatorcontrib>Zheng, Zongmei</creatorcontrib><creatorcontrib>Chen, Wanjun</creatorcontrib><creatorcontrib>Le, Anh</creatorcontrib><creatorcontrib>Shi, Songtao</creatorcontrib><creatorcontrib>Wang, Songlin</creatorcontrib><title>Allogeneic Mesenchymal Stem Cell Therapy for Bisphosphonate-Related Jaw Osteonecrosis in Swine</title><title>Stem cells and development</title><addtitle>Stem Cells Dev</addtitle><description>Bisphosphonates (BPs), which are used to treat a variety of clinical disorders, have the side effect of jawbone necrosis. Currently, there is no reliable treatment for BP-related osteonecrosis of the jaw (BRONJ) due to a lack of understanding of its pathogenesis. To investigate the pathogenesis of BRONJ and observe the treatment effect of bone marrow mesenchymal stem cell (BMMSC) transplantation, we established a preclinical animal model of BRONJ in miniature pigs (minipigs). After treatment with zoledronic acid, the clinical and radiographic manifestations of BRONJ could be observed in minipigs after first premolar extraction. The biological and immunological properties of BMMSCs were impaired in the BP-treated minipigs. Moreover, the ratio of Foxp3-positive regulatory T-cells (Tregs) in peripheral blood decreased, and interleukin (IL)-17 increased in the serum of BP-treated minipigs. After allogeneic BMMSC transplantation via intravenous infusion, mucosal healing and bone reconstruction were observed; IL-17 levels were reduced; and Tregs were elevated. In summary, we established a clinically relevant BRONJ model in minipigs and tested a promising allogeneic BMMSC-based therapy, which may have potential clinical applications for treating BRONJ.</description><subject>Animals</subject><subject>Biomarkers - metabolism</subject><subject>Bisphosphonate-Associated Osteonecrosis of the Jaw - diagnostic imaging</subject><subject>Bisphosphonate-Associated Osteonecrosis of the Jaw - pathology</subject><subject>Bisphosphonate-Associated Osteonecrosis of the Jaw - therapy</subject><subject>Diphosphonates</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Humans</subject><subject>Imidazoles</subject><subject>Interleukin-17 - blood</subject><subject>Male</subject><subject>Mandible - diagnostic imaging</subject><subject>Mandible - pathology</subject><subject>Mesenchymal Stem Cell Transplantation</subject><subject>Original Research Reports</subject><subject>Radiography</subject><subject>Swine</subject><subject>Swine, Miniature</subject><subject>T-Lymphocytes, Regulatory - pathology</subject><subject>Transplantation, Homologous</subject><issn>1547-3287</issn><issn>1557-8534</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctv1DAQhy0EoqVw5Ip85JLFr_hxQSqr8qhaVaLliuU4k66RYy92lmr_exJtqcqpB2ss-9NvZvQh9JaSFSXafKi-XzFC2YpI2j5Dx7RtVaNbLp4vd6EazrQ6Qq9q_UUIk0yLl-iIcTHTLTtGP09jzLeQIHh8CRWS3-xHF_H1BCNeQ4z4ZgPFbfd4yAV_CnW7yctJboLmO8S59Pjc3eGrOkFO4EuuoeKQ8PVdSPAavRhcrPDmvp6gH5_PbtZfm4urL9_WpxeNF5xODVW9M0Y5pxUQYfq2d1I5wr3XQsIwCNm1XitFgfZGSsWJbgfJSCcYh75T_AR9PORud90IvYc0FRfttoTRlb3NLtj_f1LY2Nv8x3JpjDZyDnh_H1Dy7x3UyY6h-nl_lyDvqqVcU0qI4QvaHNBl11pgeGhDiV2c2NmJXZzYxcnMv3s82wP9T8IM8AOwPLuUYoAOyvRE7F-HT5qr</recordid><startdate>20130715</startdate><enddate>20130715</enddate><creator>Li, Yunsheng</creator><creator>Xu, Junji</creator><creator>Mao, Lisha</creator><creator>Liu, Yi</creator><creator>Gao, Runtao</creator><creator>Zheng, Zongmei</creator><creator>Chen, Wanjun</creator><creator>Le, Anh</creator><creator>Shi, Songtao</creator><creator>Wang, Songlin</creator><general>Mary Ann Liebert, 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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20130715</creationdate><title>Allogeneic Mesenchymal Stem Cell Therapy for Bisphosphonate-Related Jaw Osteonecrosis in Swine</title><author>Li, Yunsheng ; Xu, Junji ; Mao, Lisha ; Liu, Yi ; Gao, Runtao ; Zheng, Zongmei ; Chen, Wanjun ; Le, Anh ; Shi, Songtao ; Wang, Songlin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c431t-17da997aa87e049d5da67a03cc846eff46b5c8771e1d96673085f620b423edb73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Biomarkers - metabolism</topic><topic>Bisphosphonate-Associated Osteonecrosis of the Jaw - diagnostic imaging</topic><topic>Bisphosphonate-Associated Osteonecrosis of the Jaw - pathology</topic><topic>Bisphosphonate-Associated Osteonecrosis of the Jaw - therapy</topic><topic>Diphosphonates</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>Humans</topic><topic>Imidazoles</topic><topic>Interleukin-17 - blood</topic><topic>Male</topic><topic>Mandible - diagnostic imaging</topic><topic>Mandible - pathology</topic><topic>Mesenchymal Stem Cell Transplantation</topic><topic>Original Research Reports</topic><topic>Radiography</topic><topic>Swine</topic><topic>Swine, Miniature</topic><topic>T-Lymphocytes, Regulatory - pathology</topic><topic>Transplantation, Homologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Yunsheng</creatorcontrib><creatorcontrib>Xu, Junji</creatorcontrib><creatorcontrib>Mao, Lisha</creatorcontrib><creatorcontrib>Liu, Yi</creatorcontrib><creatorcontrib>Gao, Runtao</creatorcontrib><creatorcontrib>Zheng, Zongmei</creatorcontrib><creatorcontrib>Chen, Wanjun</creatorcontrib><creatorcontrib>Le, Anh</creatorcontrib><creatorcontrib>Shi, Songtao</creatorcontrib><creatorcontrib>Wang, Songlin</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>PubMed Central (Full Participant titles)</collection><jtitle>Stem cells and development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Yunsheng</au><au>Xu, Junji</au><au>Mao, Lisha</au><au>Liu, Yi</au><au>Gao, Runtao</au><au>Zheng, Zongmei</au><au>Chen, Wanjun</au><au>Le, Anh</au><au>Shi, Songtao</au><au>Wang, Songlin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Allogeneic Mesenchymal Stem Cell Therapy for Bisphosphonate-Related Jaw Osteonecrosis in Swine</atitle><jtitle>Stem cells and development</jtitle><addtitle>Stem Cells Dev</addtitle><date>2013-07-15</date><risdate>2013</risdate><volume>22</volume><issue>14</issue><spage>247</spage><epage>2056</epage><pages>247-2056</pages><issn>1547-3287</issn><eissn>1557-8534</eissn><abstract>Bisphosphonates (BPs), which are used to treat a variety of clinical disorders, have the side effect of jawbone necrosis. Currently, there is no reliable treatment for BP-related osteonecrosis of the jaw (BRONJ) due to a lack of understanding of its pathogenesis. To investigate the pathogenesis of BRONJ and observe the treatment effect of bone marrow mesenchymal stem cell (BMMSC) transplantation, we established a preclinical animal model of BRONJ in miniature pigs (minipigs). After treatment with zoledronic acid, the clinical and radiographic manifestations of BRONJ could be observed in minipigs after first premolar extraction. The biological and immunological properties of BMMSCs were impaired in the BP-treated minipigs. Moreover, the ratio of Foxp3-positive regulatory T-cells (Tregs) in peripheral blood decreased, and interleukin (IL)-17 increased in the serum of BP-treated minipigs. After allogeneic BMMSC transplantation via intravenous infusion, mucosal healing and bone reconstruction were observed; IL-17 levels were reduced; and Tregs were elevated. In summary, we established a clinically relevant BRONJ model in minipigs and tested a promising allogeneic BMMSC-based therapy, which may have potential clinical applications for treating BRONJ.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>23461552</pmid><doi>10.1089/scd.2012.0615</doi><tpages>1810</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Biomarkers - metabolism Bisphosphonate-Associated Osteonecrosis of the Jaw - diagnostic imaging Bisphosphonate-Associated Osteonecrosis of the Jaw - pathology Bisphosphonate-Associated Osteonecrosis of the Jaw - therapy Diphosphonates Disease Models, Animal Female Forkhead Transcription Factors - metabolism Humans Imidazoles Interleukin-17 - blood Male Mandible - diagnostic imaging Mandible - pathology Mesenchymal Stem Cell Transplantation Original Research Reports Radiography Swine Swine, Miniature T-Lymphocytes, Regulatory - pathology Transplantation, Homologous |
| title | Allogeneic Mesenchymal Stem Cell Therapy for Bisphosphonate-Related Jaw Osteonecrosis in Swine |
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