Mesenchymal Stem Cell-Mediated Functional Tooth Regeneration in Swine
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{"title"=>"Mesenchymal stem cell-mediated functional tooth regeneration in Swine", "type"=>"journal", "authors"=>[{"first_name"=>"Wataru", "last_name"=>"Sonoyama", "scopus_author_id"=>"12447072100"}, {"first_name"=>"Yi", "last_name"=>"Liu", "scopus_author_id"=>"55742204100"}, {"first_name"=>"Dianji", "last_name"=>"Fang", "scopus_author_id"=>"16202700700"}, {"first_name"=>"Takayoshi", "last_name"=>"Yamaza", "scopus_author_id"=>"55951977500"}, {"first_name"=>"Byoung Moo", "last_name"=>"Seo", "scopus_author_id"=>"7007032304"}, {"first_name"=>"Chunmei", "last_name"=>"Zhang", "scopus_author_id"=>"55532836900"}, {"first_name"=>"He", "last_name"=>"Liu", "scopus_author_id"=>"8748087600"}, {"first_name"=>"Stan", "last_name"=>"Gronthos", "scopus_author_id"=>"6603773587"}, {"first_name"=>"Cun Yu", "last_name"=>"Wang", "scopus_author_id"=>"35276383300"}, {"first_name"=>"Songtao", "last_name"=>"Shi", "scopus_author_id"=>"7402200823"}, {"first_name"=>"Songlin", "last_name"=>"Wang", "scopus_author_id"=>"25931214900"}], "year"=>2006, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"17183711", "isbn"=>"0906007000091", "sgr"=>"47249094683", "scopus"=>"2-s2.0-47249094683", "issn"=>"19326203", "pui"=>"352571173", "doi"=>"10.1371/journal.pone.0000079"}, "id"=>"1ede12d8-cde1-3572-8a0c-cddbd5aaa913", "abstract"=>"Mesenchymal stem cell-mediated tissue regeneration is a promising approach for regenerative medicine for a wide range of applications. Here we report a new population of stem cells isolated from the root apical papilla of human teeth (SCAP, stem cells from apical papilla). Using a minipig model, we transplanted both human SCAP and periodontal ligament stem cells (PDLSCs) to generate a root/periodontal complex capable of supporting a porcelain crown, resulting in normal tooth function. This work integrates a stem cell-mediated tissue regeneration strategy, engineered materials for structure, and current dental crown technologies. This hybridized tissue engineering approach led to recovery of tooth strength and appearance.", "link"=>"http://www.mendeley.com/research/mesenchymal-stem-cellmediated-functional-tooth-regeneration-swine", "reader_count"=>185, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>11, "Student > Doctoral Student"=>11, "Researcher"=>26, "Student > Ph. D. Student"=>40, "Student > Postgraduate"=>16, "Student > Master"=>43, "Other"=>10, "Student > Bachelor"=>18, "Lecturer"=>5, "Professor"=>5}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>11, "Student > Doctoral Student"=>11, "Researcher"=>26, "Student > Ph. D. Student"=>40, "Student > Postgraduate"=>16, "Student > Master"=>43, "Other"=>10, "Student > Bachelor"=>18, "Lecturer"=>5, "Professor"=>5}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>72, "Chemistry"=>1, "Computer Science"=>1, "Engineering"=>10, "Environmental Science"=>1, "Nursing and Health Professions"=>1, "Biochemistry, Genetics and Molecular Biology"=>5, "Materials Science"=>6, "Medicine and Dentistry"=>83, "Physics and Astronomy"=>1, "Psychology"=>1, "Social Sciences"=>1, "Immunology and Microbiology"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "reader_count_by_subdiscipline"=>{"Materials Science"=>{"Materials Science"=>6}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>83}, "Social Sciences"=>{"Social Sciences"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Psychology"=>{"Psychology"=>1}, "Environmental Science"=>{"Environmental Science"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Engineering"=>{"Engineering"=>10}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>72}, "Computer Science"=>{"Computer Science"=>1}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}}, "reader_count_by_country"=>{"Colombia"=>2, "South Korea"=>1, "Turkey"=>1, "Korea (South)"=>1, "Iran"=>2, "United States"=>2, "Japan"=>1, "Brazil"=>3, "United Kingdom"=>2, "France"=>3, "Germany"=>1, "India"=>1}, "group_count"=>4}

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  • {"files"=>["https://ndownloader.figshare.com/files/955162"], "description"=>"<div><p>(<b>A</b>) Western blot analysis to confirm protein expression of genes identified in microarray studies showed greater abundance of survivin in SCAP than in DPSCs, with similar levels of DSP and Cbfa1/Runx2.</p>\n <p>(<b>B</b>) Flow cytometric analysis showed that <i>ex vivo</i> expanded SCAP contained approximately 7.5% CD24-positive cells, but DPSCs exhibited 0.5% positive staining for CD 24.</p>\n <p>(<b>C</b>) The proliferation rates of SCAP and DPSCs, derived from the same tooth, were assessed by co-culture with BrdU for 6 hours.</p>\n <p>The number of BrdU-positive cells was presented as a percentage of the total number of cells counted from five replicate cultures.</p>\n <p>SCAP showed a significantly higher proliferation rate in comparison with DPSCs (<b>*</b><i>P</i> = 0.0042).</p>\n <p>(<b>D</b>) Single colony-derived SCAP were able to proliferate to over 70 population doublings, which was significantly higher than DPSCs (<b>*</b><i>P</i> = 0.0192).</p>\n <p>(<b>E</b>) Dentin regeneration capacity of SCAP was significantly higher than that of DPSCs when transplanted into the same immunocompromised mice (<b>*</b><i>P</i> = 0.0489) using Scion Image analysis system (Scion Image, Rockville, MD).</p>\n <p>(<b>F</b>) SCAP showed a significant higher telomerase activity than DPSCs at passage 1 (<b>*</b><i>P</i> = 0.015).</p>\n <p>Cultured BMMSCs at passage 1 were used as a negative control to show an absence of telomerase activity.</p>\n <p>The telomerase activity was assessed by real time PCR based quantitative telomerase detection kit as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000079#s4\" target=\"_blank\">Materials and Methods</a>.</p>\n <p>(<b>G</b>) Cell motility assessed by a scratch assay.</p>\n <p>A representative area of SCAP and DPSCs at 72 hours after scratch was presented.</p>\n <p>Red arrows indicate the ranges of cell migration during 72 hours (<b>*</b><i>P</i> = 0.0033).</p></div>", "links"=>[], "tags"=>["scap"], "article_id"=>625448, "categories"=>["Biotechnology"], "users"=>["Wataru Sonoyama", "Yi Liu", "Dianji Fang", "Takayoshi Yamaza", "Byoung-Moo Seo", "Chunmei Zhang", "He Liu", "Stan Gronthos", "Cun-Yu Wang", "Songtao Shi", "Songlin Wang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000079.g002", "stats"=>{"downloads"=>2, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characterization_of_human_SCAP_in_comparison_with_DPSCs_/625448", "title"=>"Characterization of human SCAP in comparison with DPSCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:03:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/955249"], "description"=>"<div><p>(<b>A</b>) Flow cytometric analysis of cultured SCAP at passage 1 revealed expression of STRO-1 (18.12%), CD146 (72.3%), CD24 (7.56%), CD166 (93.74%), CD73 (94.14%), CD90 (95.54%), CD105 (9.23%), CD106 (32.7%), CD29 (88.1%) and ALP (11.43%), but was negative for surface molecules CD18, CD14, CD34, CD45, and CD 150.</p>\n <p>(<b>B</b>) After 2 weeks osteo-induction <i>in vitro</i> with L-ascorbate-2-phosphate, dexamethasone, and inorganic phosphate, SCAP differentiated into odontoblasts with a decrease in CD24 expression from 7.56% to 0.22%.</p>\n <p>In contrast, ALP expression increased significantly from 11.43% to 86.59%.</p></div>", "links"=>[], "tags"=>["characterization"], "article_id"=>625537, "categories"=>["Biotechnology"], "users"=>["Wataru Sonoyama", "Yi Liu", "Dianji Fang", "Takayoshi Yamaza", "Byoung-Moo Seo", "Chunmei Zhang", "He Liu", "Stan Gronthos", "Cun-Yu Wang", "Songtao Shi", "Songlin Wang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000079.g003", "stats"=>{"downloads"=>2, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Surface_Molecule_Characterization_of_human_SCAP_/625537", "title"=>"Surface Molecule Characterization of human SCAP.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:04:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/955481"], "description"=>"<div><p>(<b>A</b>) Extracted minipig lower incisor and root-shaped HA/TCP carrier loaded with SCAP.</p>\n <p>(<b>B</b>) Gelfoam containing 10×10<sup>6</sup> PDLSCs (open arrow) was used to cover the HA/SCAP (black arrow) and implanted into the lower incisor socket (open triangle).</p>\n <p>(<b>C</b>) HA/SCAP-Gelfoam/PDLSCs were implanted into a newly extracted incisor socket.</p>\n <p>A post channel was pre-created inside the root shape HA carrier (arrow).</p>\n <p>(<b>D</b>) The post channel was sealed with a temporary filling for affixing a porcelain crown in the next step.</p>\n <p>(<b>E</b>) The HA/SCAP-Gelfoam/PDLSC implant was sutured for 3 months.</p>\n <p>(<b>F</b>) The HA/SCAP-Gelfoam/PDLSC implant (arrow) was re-exposed and the temporary filling was removed to expose the post channel.</p>\n <p>(<b>G</b>) A pre-made porcelain crown was cemented to the HA/SCAP-Gelfoam/PDLSC structure.</p>\n <p>(<b>H</b>) The exposed section was sutured.</p>\n <p>(<b>I</b> and <b>J</b>) Four weeks after fixation, the porcelain crown was retained in the swine after normal tooth use as shown by open arrows.</p>\n <p>(<b>K</b>) After 3 months implantation, the HA/SCAP-Gelfoam/PDLSC implant had formed a hard root structure (open arrows) in the mandibular incisor area as shown by CT scan image.</p>\n <p>A clear PDL space was found between the implant and surrounding bony tissue (triangle arrows).</p>\n <p>(<b>L</b> and <b>M</b>) H&E staining showed that implanted HA/SCAP-Gelfoam/PDLSC contains newly regenerated dentin (<i>D</i>) inside the implant (<b>L</b>) and PDL tissue (<i>PDL</i>) on the outside of the implant (<b>M</b>).</p>\n <p>(<b>N</b>) Compressive strength measurement showed that newly formed bio-roots have much higher compressive strength than original HA/TCP carrier (<b>*</b><i>P</i> = 0.0002), but lower than that in natural swine root dentin (<b>*</b><i>P</i> = 0.003) (NR: natural minipig root, BR: newly formed bio-root, HA: original HA carrier).</p></div>", "links"=>[], "tags"=>["crown", "restoration"], "article_id"=>625762, "categories"=>["Biotechnology"], "users"=>["Wataru Sonoyama", "Yi Liu", "Dianji Fang", "Takayoshi Yamaza", "Byoung-Moo Seo", "Chunmei Zhang", "He Liu", "Stan Gronthos", "Cun-Yu Wang", "Songtao Shi", "Songlin Wang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000079.g005", "stats"=>{"downloads"=>6, "page_views"=>207, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Swine_SCAP_PDLSC_mediated_root_periodontal_structure_as_an_artificial_crown_support_for_the_restoration_of_tooth_function_in_swine_/625762", "title"=>"Swine SCAP/PDLSC-mediated root/periodontal structure as an artificial crown support for the restoration of tooth function in swine.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:06:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/955376"], "description"=>"<div><p>(<b>A</b>) On the outside of the HA/TCP carrier (<i>HA</i>), PDLSCs can form structures resembling Sharpey's fibers (arrows) connecting with newly formed cementum (<i>C</i>) on the surface of HA/TCP particles (<i>HA</i>).</p>\n <p>(<b>B</b>) Immunohistochemical staining showed that SCAP/PDLSC-generated tissues were positive for human specific mitochondria antibody staining (arrows).</p></div>", "links"=>[], "tags"=>["biotechnology/bioengineering"], "article_id"=>625659, "categories"=>["Biotechnology"], "users"=>["Wataru Sonoyama", "Yi Liu", "Dianji Fang", "Takayoshi Yamaza", "Byoung-Moo Seo", "Chunmei Zhang", "He Liu", "Stan Gronthos", "Cun-Yu Wang", "Songtao Shi", "Songlin Wang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000079.g004", "stats"=>{"downloads"=>2, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comined_human_SCAP_PDLSC_mediated_tissue_regeneration_/625659", "title"=>"Comined human SCAP/PDLSC-mediated tissue regeneration.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:05:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/955015"], "description"=>"<div><p>(<b>A</b>) Human apical papilla tissue was positive for STRO-1, an early mesenchymal progenitor marker, staining by immunofluorescence (arrows).</p>\n <p>(<b>B)</b> Single colonies were formed after human SCAP were plated at a low density (5×10<sup>3</sup>/T25 flask) and cultured for 10 days.</p>\n <p>(<b>C</b>) When human SCAP were cultured in odontogenic/osteogenic inductive conditions containing L-ascorbate-2-phosphate, dexamethasone, and inorganic phosphate for 4 weeks, mineralized nodules were found by Alizarin red S staining.</p>\n <p>(<b>D</b>) Cultured human SCAP formed Oil red O positive lipid clusters following 5 weeks of adipogenic induction in the presence of 0.5 mM isobutylmethylxanthine, 0.5 µM hydrocortisone, 60 µM indomethacin, and 10 µg/ml insulin.</p>\n <p>(<b>E</b>) Eight weeks after transplantation in immunocompromised mice, human SCAP differentiated into odontoblasts (arrows) that formed dentin (<i>D</i>) on the surfaces of a hydroxyapatite tricalcium (<i>HA</i>) carrier.</p>\n <p>(<b>F</b>) Immunohistochemical staining showed that human SCAP differentiated into odontoblasts (arrows) that were positive for anti-human specific mitochondria antibody staining.</p>\n <p>(<b>G</b>) Immunohistochemical staining showed that human SCAP-generated dentin (<i>D</i>) was positive for anti-DSP antibody staining (arrows).</p>\n <p>(<b>H</b>) Pre-immunoserum negative control of human SCAP transplant.</p>\n <p>(<b>I</b>) SCAP isolated from swine were capable of forming a single colony cluster when plated at a low cell density.</p>\n <p>(<b>J</b>) When transplanted into immunocompromised mice for 8 weeks, swine SCAP differentiate into odontoblasts (arrows) to regenerate dentin (<i>D</i>) on the surface of the hydroxyapatite carrier (<i>HA</i>).</p>\n <p>(<b>K</b>) Swine PDLSCs were capable of forming a single colony cluster.</p>\n <p>(<b>L</b>) After transplantation into immunocompromised mice, swine PDLSCs formed cementum (<i>C</i>) on the surface of hydroxyapatite carrier (<i>HA</i>).</p>\n <p>Collagen fibers were found to connect to newly formed cementum.</p></div>", "links"=>[], "tags"=>["cells", "apical", "papilla"], "article_id"=>625303, "categories"=>["Biotechnology"], "users"=>["Wataru Sonoyama", "Yi Liu", "Dianji Fang", "Takayoshi Yamaza", "Byoung-Moo Seo", "Chunmei Zhang", "He Liu", "Stan Gronthos", "Cun-Yu Wang", "Songtao Shi", "Songlin Wang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0000079.g001", "stats"=>{"downloads"=>3, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Isolation_of_Stem_Cells_from_Root_Apical_Papilla_SCAP_/625303", "title"=>"Isolation of Stem Cells from Root Apical Papilla (SCAP).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 13:02:44"}

PMC Usage Stats | Further Information

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  • {"month"=>"12", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"95", "year"=>"2009", "pdf"=>"34", "unique-ip"=>"93", "figure"=>"16", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"0", "month"=>"6", "cited-by"=>"2", "abstract"=>"2", "full-text"=>"52", "unique-ip"=>"41", "pdf"=>"17", "year"=>"2012", "figure"=>"11", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"month"=>"12", "scanned-page-browse"=>"0", "cited-by"=>"0", "abstract"=>"2", "full-text"=>"105", "year"=>"2006", "pdf"=>"99", "unique-ip"=>"94", "figure"=>"23", "scanned-summary"=>"0", "supp-data"=>"0"}
  • {"scanned-page-browse"=>"172", "month"=>"1", "cited-by"=>"14", "abstract"=>"0", "full-text"=>"4", "unique-ip"=>"99", "pdf"=>"0", "year"=>"2007", "figure"=>"603", "scanned-summary"=>"328", "supp-data"=>"271"}
  • {"month"=>"6", "scanned-page-browse"=>"75", "cited-by"=>"2", "abstract"=>"0", "full-text"=>"8", "year"=>"2007", "pdf"=>"0", "unique-ip"=>"42", "figure"=>"281", "scanned-summary"=>"156", "supp-data"=>"126"}
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  • {"unique-ip"=>"44", "full-text"=>"56", "pdf"=>"33", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"9"}
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  • {"unique-ip"=>"45", "full-text"=>"50", "pdf"=>"18", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"12"}
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  • {"unique-ip"=>"47", "full-text"=>"57", "pdf"=>"20", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"5"}
  • {"unique-ip"=>"41", "full-text"=>"42", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
  • {"unique-ip"=>"48", "full-text"=>"55", "pdf"=>"23", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
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  • {"unique-ip"=>"48", "full-text"=>"44", "pdf"=>"24", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
  • {"unique-ip"=>"31", "full-text"=>"28", "pdf"=>"19", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
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  • {"unique-ip"=>"47", "full-text"=>"48", "pdf"=>"34", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"14", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2016", "month"=>"3"}
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  • {"unique-ip"=>"50", "full-text"=>"52", "pdf"=>"34", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"22", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
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  • {"unique-ip"=>"31", "full-text"=>"37", "pdf"=>"25", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"22", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"31", "full-text"=>"31", "pdf"=>"24", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
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Relative Metric

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