Stem cell‐derived conditioned media from human exfoliated deciduous teeth promote bone regeneration

Objectives Cleft lip and palate (CL/P) are common congenital orofacial anomalies. Autogenous iliac bone grafting closes alveolar cleft defects but requires surgical intervention. Mesenchymal stem cell culture supernatant can regenerate tissues via paracrine activity. However, little is known about t...

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Veröffentlicht in:Oral diseases 2020-03, Vol.26 (2), p.381-390
Hauptverfasser: Hiraki, Tomoka, Kunimatsu, Ryo, Nakajima, Kengo, Abe, Takaharu, Yamada, Sakura, Rikitake, Kodai, Tanimoto, Kotaro
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container_end_page 390
container_issue 2
container_start_page 381
container_title Oral diseases
container_volume 26
creator Hiraki, Tomoka
Kunimatsu, Ryo
Nakajima, Kengo
Abe, Takaharu
Yamada, Sakura
Rikitake, Kodai
Tanimoto, Kotaro
description Objectives Cleft lip and palate (CL/P) are common congenital orofacial anomalies. Autogenous iliac bone grafting closes alveolar cleft defects but requires surgical intervention. Mesenchymal stem cell culture supernatant can regenerate tissues via paracrine activity. However, little is known about the bone‐regenerative effects of stem cells from human exfoliated deciduous teeth (SHED) and conditioned media (CM). Our aim was to address this. Materials and methods Stem cells were isolated from primary tooth pulp and cultured. Defects were made in calvariae of immunodeficient mice and implanted with stem cell‐ or CM‐containing atelocollagen. Regenerated bone was analysed by microcomputed tomography, haematoxylin–eosin and Masson's trichrome staining. Vascular endothelial growth factor, CD31 and CD34 expression were confirmed by immunohistochemistry, and the presence of several proteins and growth factors was verified in SHED‐CM. Results Bone regeneration was enhanced in defects treated with stem cells and CM compared to that in controls 8 weeks after transplantation. Mature bone formation and angiogenesis were confirmed with CM but not with stem cells or in controls. Secretome analysis using multiple cytokine assays revealed that SHED‐CM contained tissue‐regenerating factors with roles in angiogenesis and osteogenesis. Conclusion CM non‐invasively regenerate bone and might be effective to reconstruct alveolar clefts in CL/P patients.
doi_str_mv 10.1111/odi.13244
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Autogenous iliac bone grafting closes alveolar cleft defects but requires surgical intervention. Mesenchymal stem cell culture supernatant can regenerate tissues via paracrine activity. However, little is known about the bone‐regenerative effects of stem cells from human exfoliated deciduous teeth (SHED) and conditioned media (CM). Our aim was to address this. Materials and methods Stem cells were isolated from primary tooth pulp and cultured. Defects were made in calvariae of immunodeficient mice and implanted with stem cell‐ or CM‐containing atelocollagen. Regenerated bone was analysed by microcomputed tomography, haematoxylin–eosin and Masson's trichrome staining. Vascular endothelial growth factor, CD31 and CD34 expression were confirmed by immunohistochemistry, and the presence of several proteins and growth factors was verified in SHED‐CM. Results Bone regeneration was enhanced in defects treated with stem cells and CM compared to that in controls 8 weeks after transplantation. Mature bone formation and angiogenesis were confirmed with CM but not with stem cells or in controls. Secretome analysis using multiple cytokine assays revealed that SHED‐CM contained tissue‐regenerating factors with roles in angiogenesis and osteogenesis. Conclusion CM non‐invasively regenerate bone and might be effective to reconstruct alveolar clefts in CL/P patients.</description><identifier>ISSN: 1354-523X</identifier><identifier>EISSN: 1601-0825</identifier><identifier>DOI: 10.1111/odi.13244</identifier><identifier>PMID: 31808229</identifier><language>eng</language><publisher>Denmark: Wiley Subscription Services, Inc</publisher><subject>Alveolar bone ; Angiogenesis ; Animals ; Atelocollagen ; Bone grafts ; Bone growth ; bone regeneration ; Bone Regeneration - drug effects ; CD34 antigen ; Cell culture ; Child ; Cleft Lip - surgery ; Cleft lip/palate ; Cleft Palate - surgery ; Computed tomography ; conditioned media ; Culture Media, Conditioned - pharmacology ; Defects ; Dental pulp ; Dental Pulp - physiology ; Dentistry ; exfoliated deciduous teeth ; Growth factors ; Humans ; Immunodeficiency ; Immunohistochemistry ; Male ; Mesenchyme ; Mice ; Mice, Inbred BALB C ; Osteogenesis ; Osteogenesis - drug effects ; Paracrine signalling ; Regeneration ; Secretome ; Stem cell transplantation ; Stem cells ; Stem Cells - physiology ; Tooth Exfoliation ; Tooth, Deciduous - cytology ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - metabolism ; X-Ray Microtomography</subject><ispartof>Oral diseases, 2020-03, Vol.26 (2), p.381-390</ispartof><rights>2019 John Wiley &amp; Sons A/S. Published by John Wiley &amp; Sons Ltd. All rights reserved</rights><rights>2019 John Wiley &amp; Sons A/S. Published by John Wiley &amp; Sons Ltd. 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Autogenous iliac bone grafting closes alveolar cleft defects but requires surgical intervention. Mesenchymal stem cell culture supernatant can regenerate tissues via paracrine activity. However, little is known about the bone‐regenerative effects of stem cells from human exfoliated deciduous teeth (SHED) and conditioned media (CM). Our aim was to address this. Materials and methods Stem cells were isolated from primary tooth pulp and cultured. Defects were made in calvariae of immunodeficient mice and implanted with stem cell‐ or CM‐containing atelocollagen. Regenerated bone was analysed by microcomputed tomography, haematoxylin–eosin and Masson's trichrome staining. Vascular endothelial growth factor, CD31 and CD34 expression were confirmed by immunohistochemistry, and the presence of several proteins and growth factors was verified in SHED‐CM. Results Bone regeneration was enhanced in defects treated with stem cells and CM compared to that in controls 8 weeks after transplantation. Mature bone formation and angiogenesis were confirmed with CM but not with stem cells or in controls. Secretome analysis using multiple cytokine assays revealed that SHED‐CM contained tissue‐regenerating factors with roles in angiogenesis and osteogenesis. Conclusion CM non‐invasively regenerate bone and might be effective to reconstruct alveolar clefts in CL/P patients.</description><subject>Alveolar bone</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Atelocollagen</subject><subject>Bone grafts</subject><subject>Bone growth</subject><subject>bone regeneration</subject><subject>Bone Regeneration - drug effects</subject><subject>CD34 antigen</subject><subject>Cell culture</subject><subject>Child</subject><subject>Cleft Lip - surgery</subject><subject>Cleft lip/palate</subject><subject>Cleft Palate - surgery</subject><subject>Computed tomography</subject><subject>conditioned media</subject><subject>Culture Media, Conditioned - pharmacology</subject><subject>Defects</subject><subject>Dental pulp</subject><subject>Dental Pulp - physiology</subject><subject>Dentistry</subject><subject>exfoliated deciduous teeth</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Immunodeficiency</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>Mesenchyme</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Osteogenesis</subject><subject>Osteogenesis - drug effects</subject><subject>Paracrine signalling</subject><subject>Regeneration</subject><subject>Secretome</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Stem Cells - physiology</subject><subject>Tooth Exfoliation</subject><subject>Tooth, Deciduous - cytology</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><subject>X-Ray Microtomography</subject><issn>1354-523X</issn><issn>1601-0825</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMtKxDAUhoMoOl4WvoAE3Oii2iRN0yzF64AwCxXclVxONUPbjGnrZecj-Iw-iRlndCGYTQ7ky8d_foR2SXpE4jn21h0RRrNsBY1InpIkLShfjTPjWcIpu99Am103TVMiJKPraIORIiJUjhDc9NBgA3X9-f5hIbhnsNj41rre-TbODVincBV8gx-HRrUYXitfO9XHNwvG2cEPHe4B-kc8i5TvAev4Ewd4gBaCmnu20Vql6g52lvcWurs4vz29Sq4nl-PTk-vEZERmiSCMKa1yIS0nnBptrGZWCyWNskoXVGpRUcalBlEZQ2WeEVNlRSFAgMwl20IHC29M8jRA15eN6-bLqRZizJIySkXGeUEjuv8HnfohtDFdpHjOJRfFXHi4oEzwXRegKmfBNSq8lSQt592Xsfvyu_vI7i2Ng46t_ZI_ZUfgeAG8uBre_jeVk7PxQvkFY-qQCA</recordid><startdate>202003</startdate><enddate>202003</enddate><creator>Hiraki, Tomoka</creator><creator>Kunimatsu, Ryo</creator><creator>Nakajima, Kengo</creator><creator>Abe, Takaharu</creator><creator>Yamada, Sakura</creator><creator>Rikitake, Kodai</creator><creator>Tanimoto, Kotaro</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>7QP</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5016-4957</orcidid></search><sort><creationdate>202003</creationdate><title>Stem cell‐derived conditioned media from human exfoliated deciduous teeth promote bone regeneration</title><author>Hiraki, Tomoka ; 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Calcified Tissue Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Oral diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hiraki, Tomoka</au><au>Kunimatsu, Ryo</au><au>Nakajima, Kengo</au><au>Abe, Takaharu</au><au>Yamada, Sakura</au><au>Rikitake, Kodai</au><au>Tanimoto, Kotaro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stem cell‐derived conditioned media from human exfoliated deciduous teeth promote bone regeneration</atitle><jtitle>Oral diseases</jtitle><addtitle>Oral Dis</addtitle><date>2020-03</date><risdate>2020</risdate><volume>26</volume><issue>2</issue><spage>381</spage><epage>390</epage><pages>381-390</pages><issn>1354-523X</issn><eissn>1601-0825</eissn><abstract>Objectives Cleft lip and palate (CL/P) are common congenital orofacial anomalies. Autogenous iliac bone grafting closes alveolar cleft defects but requires surgical intervention. Mesenchymal stem cell culture supernatant can regenerate tissues via paracrine activity. However, little is known about the bone‐regenerative effects of stem cells from human exfoliated deciduous teeth (SHED) and conditioned media (CM). Our aim was to address this. Materials and methods Stem cells were isolated from primary tooth pulp and cultured. Defects were made in calvariae of immunodeficient mice and implanted with stem cell‐ or CM‐containing atelocollagen. Regenerated bone was analysed by microcomputed tomography, haematoxylin–eosin and Masson's trichrome staining. Vascular endothelial growth factor, CD31 and CD34 expression were confirmed by immunohistochemistry, and the presence of several proteins and growth factors was verified in SHED‐CM. Results Bone regeneration was enhanced in defects treated with stem cells and CM compared to that in controls 8 weeks after transplantation. Mature bone formation and angiogenesis were confirmed with CM but not with stem cells or in controls. Secretome analysis using multiple cytokine assays revealed that SHED‐CM contained tissue‐regenerating factors with roles in angiogenesis and osteogenesis. Conclusion CM non‐invasively regenerate bone and might be effective to reconstruct alveolar clefts in CL/P patients.</abstract><cop>Denmark</cop><pub>Wiley Subscription Services, Inc</pub><pmid>31808229</pmid><doi>10.1111/odi.13244</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-5016-4957</orcidid></addata></record>
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subjects Alveolar bone
Angiogenesis
Animals
Atelocollagen
Bone grafts
Bone growth
bone regeneration
Bone Regeneration - drug effects
CD34 antigen
Cell culture
Child
Cleft Lip - surgery
Cleft lip/palate
Cleft Palate - surgery
Computed tomography
conditioned media
Culture Media, Conditioned - pharmacology
Defects
Dental pulp
Dental Pulp - physiology
Dentistry
exfoliated deciduous teeth
Growth factors
Humans
Immunodeficiency
Immunohistochemistry
Male
Mesenchyme
Mice
Mice, Inbred BALB C
Osteogenesis
Osteogenesis - drug effects
Paracrine signalling
Regeneration
Secretome
Stem cell transplantation
Stem cells
Stem Cells - physiology
Tooth Exfoliation
Tooth, Deciduous - cytology
Vascular endothelial growth factor
Vascular Endothelial Growth Factor A - metabolism
X-Ray Microtomography
title Stem cell‐derived conditioned media from human exfoliated deciduous teeth promote bone regeneration
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