Mesenchymal Stem Cell‐Dependent Formation of Heterotopic Tendon‐Bone Insertions (Osteotendinous Junctions)
Ligament‐to‐bone and tendon‐to‐bone interfaces (entheses, osteotendinous junctions [OTJs]) serve to dissipate stress between soft tissue and bone. Surgical reconstruction of these interfaces is an issue of considerable importance as they are prone to injury and the integration of bone and tendon/lig...
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| Veröffentlicht in: | Stem cells (Dayton, Ohio) Ohio), 2010-09, Vol.28 (9), p.1590-1601 |
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| creator | Shahab‐Osterloh, Sandra Witte, Frank Hoffmann, Andrea Winkel, Andreas Laggies, Sandra Neumann, Berit Seiffart, Virginia Lindenmaier, Werner Gruber, Achim D. Ringe, Jochen Häupl, Thomas Thorey, Fritz Willbold, Elmar Corbeau, Pierre Gross, Gerhard |
| description | Ligament‐to‐bone and tendon‐to‐bone interfaces (entheses, osteotendinous junctions [OTJs]) serve to dissipate stress between soft tissue and bone. Surgical reconstruction of these interfaces is an issue of considerable importance as they are prone to injury and the integration of bone and tendon/ligament is in general not satisfactory. We report here the stem cell‐dependent spontaneous formation of fibrocartilaginous and fibrous entheses in heterotopic locations of the mouse if progenitors possess a tenogenic and osteo‐/chondrogenic capacity. This study followed the hypothesis that enhanced Bone Morphogenetic Protein (BMP)‐signaling in adult mesenchymal stem cells that are induced for tendon formation may overcome the tendon‐inherent interference with bone formation and may thus allow the stem cell‐dependent formation of tendon‐bone interfaces. The tenogenic and osteo‐/chondrogenic competence was mediated by the adeno‐ and/or lentiviral expression of the biologically active Smad8 signaling mediator (Smad8ca) and of Bone Morphogenetic Protein 2 (BMP2). Modified mesenchymal progenitors were implanted in subcutaneous or intramuscular sites of the mouse. The stem cell‐dependent enthesis formation was characterized histologically by immunohistological approaches and by in situ hybridization. Transplantation of modified murine stem cells resulted in the formation of tendinous and osseous structures exhibiting fibrocartilage‐type OTJs, while, in contrast, the viral modification of primary human bone marrow‐derived mesenchymal stromal/stem cells showed evidence of fibrous tendon‐bone interface formation. Moreover, it could be demonstrated that Smad8ca expression alone was sufficient for the formation of tendon/ligament‐like structures. These findings may contribute to the establishment of stem cell‐dependent regenerative therapies involving tendon/ligaments and to the improvement of the insertion of tendon grafts at bony attachment sites, eventually. STEM CELLS 2010; 28:1590–1601. |
| doi_str_mv | 10.1002/stem.487 |
| format | Article |
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Surgical reconstruction of these interfaces is an issue of considerable importance as they are prone to injury and the integration of bone and tendon/ligament is in general not satisfactory. We report here the stem cell‐dependent spontaneous formation of fibrocartilaginous and fibrous entheses in heterotopic locations of the mouse if progenitors possess a tenogenic and osteo‐/chondrogenic capacity. This study followed the hypothesis that enhanced Bone Morphogenetic Protein (BMP)‐signaling in adult mesenchymal stem cells that are induced for tendon formation may overcome the tendon‐inherent interference with bone formation and may thus allow the stem cell‐dependent formation of tendon‐bone interfaces. The tenogenic and osteo‐/chondrogenic competence was mediated by the adeno‐ and/or lentiviral expression of the biologically active Smad8 signaling mediator (Smad8ca) and of Bone Morphogenetic Protein 2 (BMP2). Modified mesenchymal progenitors were implanted in subcutaneous or intramuscular sites of the mouse. The stem cell‐dependent enthesis formation was characterized histologically by immunohistological approaches and by in situ hybridization. Transplantation of modified murine stem cells resulted in the formation of tendinous and osseous structures exhibiting fibrocartilage‐type OTJs, while, in contrast, the viral modification of primary human bone marrow‐derived mesenchymal stromal/stem cells showed evidence of fibrous tendon‐bone interface formation. Moreover, it could be demonstrated that Smad8ca expression alone was sufficient for the formation of tendon/ligament‐like structures. These findings may contribute to the establishment of stem cell‐dependent regenerative therapies involving tendon/ligaments and to the improvement of the insertion of tendon grafts at bony attachment sites, eventually. STEM CELLS 2010; 28:1590–1601.</description><identifier>ISSN: 1066-5099</identifier><identifier>EISSN: 1549-4918</identifier><identifier>DOI: 10.1002/stem.487</identifier><identifier>PMID: 20882636</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adenoviridae - genetics ; Adult Stem Cells - metabolism ; Adult Stem Cells - transplantation ; Animals ; bone ; Bone and Bones - metabolism ; Bone Morphogenetic Protein 2 - genetics ; Bone Morphogenetic Protein 2 - metabolism ; Cells, Cultured ; Chondrogenesis ; Female ; Fibrocartilage - growth & development ; Fibrocartilage - metabolism ; Gene therapy ; Genetic Vectors ; Genetics ; Humans ; Lentivirus - genetics ; Life Sciences ; Marrow stromal stem cells ; Mesenchymal Stem Cell Transplantation ; Mesenchymal stem cells ; Mesenchymal Stem Cells - metabolism ; Mice ; Mice, Inbred C3H ; Mice, Nude ; Ossification, Heterotopic ; Osteogenesis ; Rats ; Signal transduction ; Skeleton ; Smad8 Protein - genetics ; Smad8 Protein - metabolism ; Somatic cell therapy ; tendon ; Tendons - growth & development ; Tendons - metabolism ; Time Factors ; Tissue Engineering ; Transduction, Genetic ; Transplantation, Heterotopic</subject><ispartof>Stem cells (Dayton, Ohio), 2010-09, Vol.28 (9), p.1590-1601</ispartof><rights>Copyright © 2010 AlphaMed Press</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4207-648a15c1a3ceccbde0f00685f1340e9c1d72fdcdc3c7f05a597f578db9ac830a3</citedby><cites>FETCH-LOGICAL-c4207-648a15c1a3ceccbde0f00685f1340e9c1d72fdcdc3c7f05a597f578db9ac830a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20882636$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-00529327$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Shahab‐Osterloh, Sandra</creatorcontrib><creatorcontrib>Witte, Frank</creatorcontrib><creatorcontrib>Hoffmann, Andrea</creatorcontrib><creatorcontrib>Winkel, Andreas</creatorcontrib><creatorcontrib>Laggies, Sandra</creatorcontrib><creatorcontrib>Neumann, Berit</creatorcontrib><creatorcontrib>Seiffart, Virginia</creatorcontrib><creatorcontrib>Lindenmaier, Werner</creatorcontrib><creatorcontrib>Gruber, Achim D.</creatorcontrib><creatorcontrib>Ringe, Jochen</creatorcontrib><creatorcontrib>Häupl, Thomas</creatorcontrib><creatorcontrib>Thorey, Fritz</creatorcontrib><creatorcontrib>Willbold, Elmar</creatorcontrib><creatorcontrib>Corbeau, Pierre</creatorcontrib><creatorcontrib>Gross, Gerhard</creatorcontrib><title>Mesenchymal Stem Cell‐Dependent Formation of Heterotopic Tendon‐Bone Insertions (Osteotendinous Junctions)</title><title>Stem cells (Dayton, Ohio)</title><addtitle>Stem Cells</addtitle><description>Ligament‐to‐bone and tendon‐to‐bone interfaces (entheses, osteotendinous junctions [OTJs]) serve to dissipate stress between soft tissue and bone. Surgical reconstruction of these interfaces is an issue of considerable importance as they are prone to injury and the integration of bone and tendon/ligament is in general not satisfactory. We report here the stem cell‐dependent spontaneous formation of fibrocartilaginous and fibrous entheses in heterotopic locations of the mouse if progenitors possess a tenogenic and osteo‐/chondrogenic capacity. This study followed the hypothesis that enhanced Bone Morphogenetic Protein (BMP)‐signaling in adult mesenchymal stem cells that are induced for tendon formation may overcome the tendon‐inherent interference with bone formation and may thus allow the stem cell‐dependent formation of tendon‐bone interfaces. The tenogenic and osteo‐/chondrogenic competence was mediated by the adeno‐ and/or lentiviral expression of the biologically active Smad8 signaling mediator (Smad8ca) and of Bone Morphogenetic Protein 2 (BMP2). Modified mesenchymal progenitors were implanted in subcutaneous or intramuscular sites of the mouse. The stem cell‐dependent enthesis formation was characterized histologically by immunohistological approaches and by in situ hybridization. Transplantation of modified murine stem cells resulted in the formation of tendinous and osseous structures exhibiting fibrocartilage‐type OTJs, while, in contrast, the viral modification of primary human bone marrow‐derived mesenchymal stromal/stem cells showed evidence of fibrous tendon‐bone interface formation. Moreover, it could be demonstrated that Smad8ca expression alone was sufficient for the formation of tendon/ligament‐like structures. These findings may contribute to the establishment of stem cell‐dependent regenerative therapies involving tendon/ligaments and to the improvement of the insertion of tendon grafts at bony attachment sites, eventually. 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Surgical reconstruction of these interfaces is an issue of considerable importance as they are prone to injury and the integration of bone and tendon/ligament is in general not satisfactory. We report here the stem cell‐dependent spontaneous formation of fibrocartilaginous and fibrous entheses in heterotopic locations of the mouse if progenitors possess a tenogenic and osteo‐/chondrogenic capacity. This study followed the hypothesis that enhanced Bone Morphogenetic Protein (BMP)‐signaling in adult mesenchymal stem cells that are induced for tendon formation may overcome the tendon‐inherent interference with bone formation and may thus allow the stem cell‐dependent formation of tendon‐bone interfaces. The tenogenic and osteo‐/chondrogenic competence was mediated by the adeno‐ and/or lentiviral expression of the biologically active Smad8 signaling mediator (Smad8ca) and of Bone Morphogenetic Protein 2 (BMP2). Modified mesenchymal progenitors were implanted in subcutaneous or intramuscular sites of the mouse. The stem cell‐dependent enthesis formation was characterized histologically by immunohistological approaches and by in situ hybridization. Transplantation of modified murine stem cells resulted in the formation of tendinous and osseous structures exhibiting fibrocartilage‐type OTJs, while, in contrast, the viral modification of primary human bone marrow‐derived mesenchymal stromal/stem cells showed evidence of fibrous tendon‐bone interface formation. Moreover, it could be demonstrated that Smad8ca expression alone was sufficient for the formation of tendon/ligament‐like structures. These findings may contribute to the establishment of stem cell‐dependent regenerative therapies involving tendon/ligaments and to the improvement of the insertion of tendon grafts at bony attachment sites, eventually. STEM CELLS 2010; 28:1590–1601.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>20882636</pmid><doi>10.1002/stem.487</doi><tpages>12</tpages></addata></record> |
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| ispartof | Stem cells (Dayton, Ohio), 2010-09, Vol.28 (9), p.1590-1601 |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adenoviridae - genetics Adult Stem Cells - metabolism Adult Stem Cells - transplantation Animals bone Bone and Bones - metabolism Bone Morphogenetic Protein 2 - genetics Bone Morphogenetic Protein 2 - metabolism Cells, Cultured Chondrogenesis Female Fibrocartilage - growth & development Fibrocartilage - metabolism Gene therapy Genetic Vectors Genetics Humans Lentivirus - genetics Life Sciences Marrow stromal stem cells Mesenchymal Stem Cell Transplantation Mesenchymal stem cells Mesenchymal Stem Cells - metabolism Mice Mice, Inbred C3H Mice, Nude Ossification, Heterotopic Osteogenesis Rats Signal transduction Skeleton Smad8 Protein - genetics Smad8 Protein - metabolism Somatic cell therapy tendon Tendons - growth & development Tendons - metabolism Time Factors Tissue Engineering Transduction, Genetic Transplantation, Heterotopic |
| title | Mesenchymal Stem Cell‐Dependent Formation of Heterotopic Tendon‐Bone Insertions (Osteotendinous Junctions) |
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