Periodontal regeneration using engineered bone marrow mesenchymal stromal cells

Abstract Regeneration of lost periodontium is a challenge in that both hard (alveolar bone, cementum) and soft (periodontal ligament) connective tissues need to be restored to their original architecture. Bone marrow mesenchymal stromal cells (BM-MSCs) appear to be an attractive candidate for connec...

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Veröffentlicht in:Biomaterials 2010-11, Vol.31 (33), p.8574-8582
Hauptverfasser: Yang, Yi, Rossi, Fabio M.V, Putnins, Edward E
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container_title Biomaterials
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creator Yang, Yi
Rossi, Fabio M.V
Putnins, Edward E
description Abstract Regeneration of lost periodontium is a challenge in that both hard (alveolar bone, cementum) and soft (periodontal ligament) connective tissues need to be restored to their original architecture. Bone marrow mesenchymal stromal cells (BM-MSCs) appear to be an attractive candidate for connective tissue regeneration. We hypothesized that BM-MSCs are able to sense biological cues from the local microenvironment and organize appropriately to contribute to the regeneration of both soft and hard periodontal connective tissues. To test this hypothesis, we transplanted GFP+ rat BM-MSCs expanded ex vivo on microcarrier gelatin beads into a surgically created rat periodontal defect. After three weeks, evidence of regeneration of bone, cementum and periodontal ligament was observed in both transplanted and control animals. However, the animals that received BM-MSCs regenerated significantly greater new bone. In addition, the animals that had received the cells and beads transplant had significantly more appropriately orientated periodontal ligament fibers, indicative of functional restoration. Finally, donor-derived BM-MSCs were found integrated in newly formed bone, cementum and periodontal ligament, suggesting that they can directly contribute to the regeneration of cells of these tissues.
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Bone marrow mesenchymal stromal cells (BM-MSCs) appear to be an attractive candidate for connective tissue regeneration. We hypothesized that BM-MSCs are able to sense biological cues from the local microenvironment and organize appropriately to contribute to the regeneration of both soft and hard periodontal connective tissues. To test this hypothesis, we transplanted GFP+ rat BM-MSCs expanded ex vivo on microcarrier gelatin beads into a surgically created rat periodontal defect. After three weeks, evidence of regeneration of bone, cementum and periodontal ligament was observed in both transplanted and control animals. However, the animals that received BM-MSCs regenerated significantly greater new bone. In addition, the animals that had received the cells and beads transplant had significantly more appropriately orientated periodontal ligament fibers, indicative of functional restoration. Finally, donor-derived BM-MSCs were found integrated in newly formed bone, cementum and periodontal ligament, suggesting that they can directly contribute to the regeneration of cells of these tissues.</description><identifier>ISSN: 0142-9612</identifier><identifier>EISSN: 1878-5905</identifier><identifier>DOI: 10.1016/j.biomaterials.2010.06.026</identifier><identifier>PMID: 20832109</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Acid Phosphatase - metabolism ; Adult bone marrow mesenchymal stromal cells ; Advanced Basic Science ; Animals ; Beads ; Bone marrow ; Bone Marrow Cells - cytology ; Bone Marrow Cells - drug effects ; Bones ; Cementogenesis - drug effects ; Cements ; Connective tissue ; Dental Cementum - cytology ; Dental Cementum - drug effects ; Dentistry ; Gelatin - pharmacology ; Green Fluorescent Proteins - metabolism ; In vivo ; Isoenzymes - metabolism ; Ligaments ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells - cytology ; Mesenchymal Stromal Cells - drug effects ; Microspheres ; Osteocalcin - metabolism ; Osteogenesis - drug effects ; Periodontal Ligament - cytology ; Periodontal Ligament - drug effects ; Periodontal Ligament - growth &amp; development ; Periodontal regeneration ; Periodontium - drug effects ; Periodontium - pathology ; Periodontium - physiology ; Rats ; Rats, Sprague-Dawley ; Regeneration ; Regeneration - drug effects ; Regeneration - physiology ; Restoration ; Stromal Cells - cytology ; Stromal Cells - drug effects ; Tartrate-Resistant Acid Phosphatase ; Tissue engineering ; Wound Healing - drug effects</subject><ispartof>Biomaterials, 2010-11, Vol.31 (33), p.8574-8582</ispartof><rights>Elsevier Ltd</rights><rights>2010 Elsevier Ltd</rights><rights>Copyright © 2010 Elsevier Ltd. 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Bone marrow mesenchymal stromal cells (BM-MSCs) appear to be an attractive candidate for connective tissue regeneration. We hypothesized that BM-MSCs are able to sense biological cues from the local microenvironment and organize appropriately to contribute to the regeneration of both soft and hard periodontal connective tissues. To test this hypothesis, we transplanted GFP+ rat BM-MSCs expanded ex vivo on microcarrier gelatin beads into a surgically created rat periodontal defect. After three weeks, evidence of regeneration of bone, cementum and periodontal ligament was observed in both transplanted and control animals. However, the animals that received BM-MSCs regenerated significantly greater new bone. In addition, the animals that had received the cells and beads transplant had significantly more appropriately orientated periodontal ligament fibers, indicative of functional restoration. Finally, donor-derived BM-MSCs were found integrated in newly formed bone, cementum and periodontal ligament, suggesting that they can directly contribute to the regeneration of cells of these tissues.</description><subject>Acid Phosphatase - metabolism</subject><subject>Adult bone marrow mesenchymal stromal cells</subject><subject>Advanced Basic Science</subject><subject>Animals</subject><subject>Beads</subject><subject>Bone marrow</subject><subject>Bone Marrow Cells - cytology</subject><subject>Bone Marrow Cells - drug effects</subject><subject>Bones</subject><subject>Cementogenesis - drug effects</subject><subject>Cements</subject><subject>Connective tissue</subject><subject>Dental Cementum - cytology</subject><subject>Dental Cementum - drug effects</subject><subject>Dentistry</subject><subject>Gelatin - pharmacology</subject><subject>Green Fluorescent Proteins - metabolism</subject><subject>In vivo</subject><subject>Isoenzymes - metabolism</subject><subject>Ligaments</subject><subject>Mesenchymal Stem Cell Transplantation</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Mesenchymal Stromal Cells - drug effects</subject><subject>Microspheres</subject><subject>Osteocalcin - metabolism</subject><subject>Osteogenesis - drug effects</subject><subject>Periodontal Ligament - cytology</subject><subject>Periodontal Ligament - drug effects</subject><subject>Periodontal Ligament - growth &amp; development</subject><subject>Periodontal regeneration</subject><subject>Periodontium - drug effects</subject><subject>Periodontium - pathology</subject><subject>Periodontium - physiology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Regeneration</subject><subject>Regeneration - drug effects</subject><subject>Regeneration - physiology</subject><subject>Restoration</subject><subject>Stromal Cells - cytology</subject><subject>Stromal Cells - drug effects</subject><subject>Tartrate-Resistant Acid Phosphatase</subject><subject>Tissue engineering</subject><subject>Wound Healing - drug effects</subject><issn>0142-9612</issn><issn>1878-5905</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkk2LFDEQhoMo7rj6F6Txopceq9KddOJBkPUTFlZQzyGdrhkzdidr0q3MvzfNrCIe1FMR8rz19RZjjxC2CCifHra9j5OdKXk75i2H8gFyC1zeYhtUnaqFBnGbbQBbXmuJ_Izdy_kA5Q0tv8vOOKiGI-gNu3pfssQhhtmOVaI9BUp29jFUS_ZhX1HY-0CUaKj6GKiabErxezVRpuA-H6eiynOKa3Q0jvk-u7MrTdGDm3jOPr1-9fHibX159ebdxYvL2rVaz_UOWyK9023X6kZI6FHRoGzXCGV3glRvHScnpRWgpBNKDxxtL8sESvUcXXPOHp_yXqf4daE8m8nntQMbKC7ZqFa3UrWN-CfZCSmF7hpZyCd_JVF2yFWjEQv67IS6FHNOtDPXyZfdHA2CWU0yB_O7SWY1yYA0xaQifnhTZ-knGn5Jf7pSgJcngMoGv3lKJjtf9k2DT-RmM0T_f3We_5HGjT54Z8cvdKR8iEsKqwZN5gbMh_Vc1mtBAOiUxuYH_46_AQ</recordid><startdate>20101101</startdate><enddate>20101101</enddate><creator>Yang, Yi</creator><creator>Rossi, Fabio M.V</creator><creator>Putnins, Edward E</creator><general>Elsevier Ltd</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>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>F28</scope><scope>FR3</scope><scope>JG9</scope><scope>L7M</scope><scope>7X8</scope><scope>7QO</scope><scope>P64</scope></search><sort><creationdate>20101101</creationdate><title>Periodontal regeneration using engineered bone marrow mesenchymal stromal cells</title><author>Yang, Yi ; Rossi, Fabio M.V ; Putnins, Edward E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c499t-f14ee9f947493560b18ed8a7358af5e8bac2ec66a5086c589d21ab600188b21c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Acid Phosphatase - metabolism</topic><topic>Adult bone marrow mesenchymal stromal cells</topic><topic>Advanced Basic Science</topic><topic>Animals</topic><topic>Beads</topic><topic>Bone marrow</topic><topic>Bone Marrow Cells - cytology</topic><topic>Bone Marrow Cells - drug effects</topic><topic>Bones</topic><topic>Cementogenesis - drug effects</topic><topic>Cements</topic><topic>Connective tissue</topic><topic>Dental Cementum - cytology</topic><topic>Dental Cementum - drug effects</topic><topic>Dentistry</topic><topic>Gelatin - pharmacology</topic><topic>Green Fluorescent Proteins - metabolism</topic><topic>In vivo</topic><topic>Isoenzymes - metabolism</topic><topic>Ligaments</topic><topic>Mesenchymal Stem Cell Transplantation</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Mesenchymal Stromal Cells - drug effects</topic><topic>Microspheres</topic><topic>Osteocalcin - metabolism</topic><topic>Osteogenesis - drug effects</topic><topic>Periodontal Ligament - cytology</topic><topic>Periodontal Ligament - drug effects</topic><topic>Periodontal Ligament - growth &amp; development</topic><topic>Periodontal regeneration</topic><topic>Periodontium - drug effects</topic><topic>Periodontium - pathology</topic><topic>Periodontium - physiology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Regeneration</topic><topic>Regeneration - drug effects</topic><topic>Regeneration - physiology</topic><topic>Restoration</topic><topic>Stromal Cells - cytology</topic><topic>Stromal Cells - drug effects</topic><topic>Tartrate-Resistant Acid Phosphatase</topic><topic>Tissue engineering</topic><topic>Wound Healing - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Yi</creatorcontrib><creatorcontrib>Rossi, Fabio M.V</creatorcontrib><creatorcontrib>Putnins, Edward E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Mechanical &amp; 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Bone marrow mesenchymal stromal cells (BM-MSCs) appear to be an attractive candidate for connective tissue regeneration. We hypothesized that BM-MSCs are able to sense biological cues from the local microenvironment and organize appropriately to contribute to the regeneration of both soft and hard periodontal connective tissues. To test this hypothesis, we transplanted GFP+ rat BM-MSCs expanded ex vivo on microcarrier gelatin beads into a surgically created rat periodontal defect. After three weeks, evidence of regeneration of bone, cementum and periodontal ligament was observed in both transplanted and control animals. However, the animals that received BM-MSCs regenerated significantly greater new bone. In addition, the animals that had received the cells and beads transplant had significantly more appropriately orientated periodontal ligament fibers, indicative of functional restoration. Finally, donor-derived BM-MSCs were found integrated in newly formed bone, cementum and periodontal ligament, suggesting that they can directly contribute to the regeneration of cells of these tissues.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>20832109</pmid><doi>10.1016/j.biomaterials.2010.06.026</doi><tpages>9</tpages></addata></record>
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subjects Acid Phosphatase - metabolism
Adult bone marrow mesenchymal stromal cells
Advanced Basic Science
Animals
Beads
Bone marrow
Bone Marrow Cells - cytology
Bone Marrow Cells - drug effects
Bones
Cementogenesis - drug effects
Cements
Connective tissue
Dental Cementum - cytology
Dental Cementum - drug effects
Dentistry
Gelatin - pharmacology
Green Fluorescent Proteins - metabolism
In vivo
Isoenzymes - metabolism
Ligaments
Mesenchymal Stem Cell Transplantation
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - drug effects
Microspheres
Osteocalcin - metabolism
Osteogenesis - drug effects
Periodontal Ligament - cytology
Periodontal Ligament - drug effects
Periodontal Ligament - growth & development
Periodontal regeneration
Periodontium - drug effects
Periodontium - pathology
Periodontium - physiology
Rats
Rats, Sprague-Dawley
Regeneration
Regeneration - drug effects
Regeneration - physiology
Restoration
Stromal Cells - cytology
Stromal Cells - drug effects
Tartrate-Resistant Acid Phosphatase
Tissue engineering
Wound Healing - drug effects
title Periodontal regeneration using engineered bone marrow mesenchymal stromal cells
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