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Delayed Minimally Invasive Injection of Allogenic Bone Marrow Stromal Cell Sheets Regenerates Large Bone Defects in an Ovine Preclinical Animal Model

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Zeitschriftentitel: Stem Cells Translational Medicine
Personen und Körperschaften: Berner, Arne, Henkel, Jan, Woodruff, Maria A., Steck, Roland, Nerlich, Michael, Schuetz, Michael A., Hutmacher, Dietmar W.
In: Stem Cells Translational Medicine, 4, 2015, 5, S. 503-512
Medientyp: E-Article
Sprache: Englisch
veröffentlicht:
Oxford University Press (OUP)
Schlagwörter:
author_facet Berner, Arne
Henkel, Jan
Woodruff, Maria A.
Steck, Roland
Nerlich, Michael
Schuetz, Michael A.
Hutmacher, Dietmar W.
Berner, Arne
Henkel, Jan
Woodruff, Maria A.
Steck, Roland
Nerlich, Michael
Schuetz, Michael A.
Hutmacher, Dietmar W.
author Berner, Arne
Henkel, Jan
Woodruff, Maria A.
Steck, Roland
Nerlich, Michael
Schuetz, Michael A.
Hutmacher, Dietmar W.
spellingShingle Berner, Arne
Henkel, Jan
Woodruff, Maria A.
Steck, Roland
Nerlich, Michael
Schuetz, Michael A.
Hutmacher, Dietmar W.
Stem Cells Translational Medicine
Delayed Minimally Invasive Injection of Allogenic Bone Marrow Stromal Cell Sheets Regenerates Large Bone Defects in an Ovine Preclinical Animal Model
Cell Biology
Developmental Biology
General Medicine
author_sort berner, arne
spelling Berner, Arne Henkel, Jan Woodruff, Maria A. Steck, Roland Nerlich, Michael Schuetz, Michael A. Hutmacher, Dietmar W. 2157-6564 2157-6580 Oxford University Press (OUP) Cell Biology Developmental Biology General Medicine http://dx.doi.org/10.5966/sctm.2014-0244 <jats:title>Abstract</jats:title> <jats:sec> <jats:title /> <jats:p>Cell-based tissue engineering approaches are promising strategies in the field of regenerative medicine. However, the mode of cell delivery is still a concern and needs to be significantly improved. Scaffolds and/or matrices loaded with cells are often transplanted into a bone defect immediately after the defect has been created. At this point, the nutrient and oxygen supply is low and the inflammatory cascade is incited, thus creating a highly unfavorable microenvironment for transplanted cells to survive and participate in the regeneration process. We therefore developed a unique treatment concept using the delayed injection of allogenic bone marrow stromal cell (BMSC) sheets to regenerate a critical-sized tibial defect in sheep to study the effect of the cells' regeneration potential when introduced at a postinflammatory stage. Minimally invasive percutaneous injection of allogenic BMSCs into biodegradable composite scaffolds 4 weeks after the defect surgery led to significantly improved bone regeneration compared with preseeded scaffold/cell constructs and scaffold-only groups. Biomechanical testing and microcomputed tomography showed comparable results to the clinical reference standard (i.e., an autologous bone graft). To our knowledge, we are the first to show in a validated preclinical large animal model that delayed allogenic cell transplantation can provide applicable clinical treatment alternatives for challenging bone defects in the future.</jats:p> </jats:sec> <jats:sec> <jats:title>Significance</jats:title> <jats:p>From a translational point of view, a comprehensive study is presented, the results of which show that percutaneous injection of allogenic BMSCs into the biodegradable composite scaffold 4 weeks after the defect surgery led to significantly improved bone regeneration compared with preseeded scaffold/cell constructs and scaffold-only groups. Biomechanical testing and microcomputed tomography showed results comparable to those of the clinical gold standard, namely autologous autograft. To the authors' knowledge, this is the first study to display in a validated preclinical large animal model that delayed allogenic cell transplantation could provide clinical treatment alternatives for challenging bone defects in the future.</jats:p> </jats:sec> Delayed Minimally Invasive Injection of Allogenic Bone Marrow Stromal Cell Sheets Regenerates Large Bone Defects in an Ovine Preclinical Animal Model Stem Cells Translational Medicine
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title Delayed Minimally Invasive Injection of Allogenic Bone Marrow Stromal Cell Sheets Regenerates Large Bone Defects in an Ovine Preclinical Animal Model
title_unstemmed Delayed Minimally Invasive Injection of Allogenic Bone Marrow Stromal Cell Sheets Regenerates Large Bone Defects in an Ovine Preclinical Animal Model
title_full Delayed Minimally Invasive Injection of Allogenic Bone Marrow Stromal Cell Sheets Regenerates Large Bone Defects in an Ovine Preclinical Animal Model
title_fullStr Delayed Minimally Invasive Injection of Allogenic Bone Marrow Stromal Cell Sheets Regenerates Large Bone Defects in an Ovine Preclinical Animal Model
title_full_unstemmed Delayed Minimally Invasive Injection of Allogenic Bone Marrow Stromal Cell Sheets Regenerates Large Bone Defects in an Ovine Preclinical Animal Model
title_short Delayed Minimally Invasive Injection of Allogenic Bone Marrow Stromal Cell Sheets Regenerates Large Bone Defects in an Ovine Preclinical Animal Model
title_sort delayed minimally invasive injection of allogenic bone marrow stromal cell sheets regenerates large bone defects in an ovine preclinical animal model
topic Cell Biology
Developmental Biology
General Medicine
url http://dx.doi.org/10.5966/sctm.2014-0244
publishDate 2015
physical 503-512
description <jats:title>Abstract</jats:title> <jats:sec> <jats:title /> <jats:p>Cell-based tissue engineering approaches are promising strategies in the field of regenerative medicine. However, the mode of cell delivery is still a concern and needs to be significantly improved. Scaffolds and/or matrices loaded with cells are often transplanted into a bone defect immediately after the defect has been created. At this point, the nutrient and oxygen supply is low and the inflammatory cascade is incited, thus creating a highly unfavorable microenvironment for transplanted cells to survive and participate in the regeneration process. We therefore developed a unique treatment concept using the delayed injection of allogenic bone marrow stromal cell (BMSC) sheets to regenerate a critical-sized tibial defect in sheep to study the effect of the cells' regeneration potential when introduced at a postinflammatory stage. Minimally invasive percutaneous injection of allogenic BMSCs into biodegradable composite scaffolds 4 weeks after the defect surgery led to significantly improved bone regeneration compared with preseeded scaffold/cell constructs and scaffold-only groups. Biomechanical testing and microcomputed tomography showed comparable results to the clinical reference standard (i.e., an autologous bone graft). To our knowledge, we are the first to show in a validated preclinical large animal model that delayed allogenic cell transplantation can provide applicable clinical treatment alternatives for challenging bone defects in the future.</jats:p> </jats:sec> <jats:sec> <jats:title>Significance</jats:title> <jats:p>From a translational point of view, a comprehensive study is presented, the results of which show that percutaneous injection of allogenic BMSCs into the biodegradable composite scaffold 4 weeks after the defect surgery led to significantly improved bone regeneration compared with preseeded scaffold/cell constructs and scaffold-only groups. Biomechanical testing and microcomputed tomography showed results comparable to those of the clinical gold standard, namely autologous autograft. To the authors' knowledge, this is the first study to display in a validated preclinical large animal model that delayed allogenic cell transplantation could provide clinical treatment alternatives for challenging bone defects in the future.</jats:p> </jats:sec>
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author Berner, Arne, Henkel, Jan, Woodruff, Maria A., Steck, Roland, Nerlich, Michael, Schuetz, Michael A., Hutmacher, Dietmar W.
author_facet Berner, Arne, Henkel, Jan, Woodruff, Maria A., Steck, Roland, Nerlich, Michael, Schuetz, Michael A., Hutmacher, Dietmar W., Berner, Arne, Henkel, Jan, Woodruff, Maria A., Steck, Roland, Nerlich, Michael, Schuetz, Michael A., Hutmacher, Dietmar W.
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description <jats:title>Abstract</jats:title> <jats:sec> <jats:title /> <jats:p>Cell-based tissue engineering approaches are promising strategies in the field of regenerative medicine. However, the mode of cell delivery is still a concern and needs to be significantly improved. Scaffolds and/or matrices loaded with cells are often transplanted into a bone defect immediately after the defect has been created. At this point, the nutrient and oxygen supply is low and the inflammatory cascade is incited, thus creating a highly unfavorable microenvironment for transplanted cells to survive and participate in the regeneration process. We therefore developed a unique treatment concept using the delayed injection of allogenic bone marrow stromal cell (BMSC) sheets to regenerate a critical-sized tibial defect in sheep to study the effect of the cells' regeneration potential when introduced at a postinflammatory stage. Minimally invasive percutaneous injection of allogenic BMSCs into biodegradable composite scaffolds 4 weeks after the defect surgery led to significantly improved bone regeneration compared with preseeded scaffold/cell constructs and scaffold-only groups. Biomechanical testing and microcomputed tomography showed comparable results to the clinical reference standard (i.e., an autologous bone graft). To our knowledge, we are the first to show in a validated preclinical large animal model that delayed allogenic cell transplantation can provide applicable clinical treatment alternatives for challenging bone defects in the future.</jats:p> </jats:sec> <jats:sec> <jats:title>Significance</jats:title> <jats:p>From a translational point of view, a comprehensive study is presented, the results of which show that percutaneous injection of allogenic BMSCs into the biodegradable composite scaffold 4 weeks after the defect surgery led to significantly improved bone regeneration compared with preseeded scaffold/cell constructs and scaffold-only groups. Biomechanical testing and microcomputed tomography showed results comparable to those of the clinical gold standard, namely autologous autograft. To the authors' knowledge, this is the first study to display in a validated preclinical large animal model that delayed allogenic cell transplantation could provide clinical treatment alternatives for challenging bone defects in the future.</jats:p> </jats:sec>
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spelling Berner, Arne Henkel, Jan Woodruff, Maria A. Steck, Roland Nerlich, Michael Schuetz, Michael A. Hutmacher, Dietmar W. 2157-6564 2157-6580 Oxford University Press (OUP) Cell Biology Developmental Biology General Medicine http://dx.doi.org/10.5966/sctm.2014-0244 <jats:title>Abstract</jats:title> <jats:sec> <jats:title /> <jats:p>Cell-based tissue engineering approaches are promising strategies in the field of regenerative medicine. However, the mode of cell delivery is still a concern and needs to be significantly improved. Scaffolds and/or matrices loaded with cells are often transplanted into a bone defect immediately after the defect has been created. At this point, the nutrient and oxygen supply is low and the inflammatory cascade is incited, thus creating a highly unfavorable microenvironment for transplanted cells to survive and participate in the regeneration process. We therefore developed a unique treatment concept using the delayed injection of allogenic bone marrow stromal cell (BMSC) sheets to regenerate a critical-sized tibial defect in sheep to study the effect of the cells' regeneration potential when introduced at a postinflammatory stage. Minimally invasive percutaneous injection of allogenic BMSCs into biodegradable composite scaffolds 4 weeks after the defect surgery led to significantly improved bone regeneration compared with preseeded scaffold/cell constructs and scaffold-only groups. Biomechanical testing and microcomputed tomography showed comparable results to the clinical reference standard (i.e., an autologous bone graft). To our knowledge, we are the first to show in a validated preclinical large animal model that delayed allogenic cell transplantation can provide applicable clinical treatment alternatives for challenging bone defects in the future.</jats:p> </jats:sec> <jats:sec> <jats:title>Significance</jats:title> <jats:p>From a translational point of view, a comprehensive study is presented, the results of which show that percutaneous injection of allogenic BMSCs into the biodegradable composite scaffold 4 weeks after the defect surgery led to significantly improved bone regeneration compared with preseeded scaffold/cell constructs and scaffold-only groups. Biomechanical testing and microcomputed tomography showed results comparable to those of the clinical gold standard, namely autologous autograft. To the authors' knowledge, this is the first study to display in a validated preclinical large animal model that delayed allogenic cell transplantation could provide clinical treatment alternatives for challenging bone defects in the future.</jats:p> </jats:sec> Delayed Minimally Invasive Injection of Allogenic Bone Marrow Stromal Cell Sheets Regenerates Large Bone Defects in an Ovine Preclinical Animal Model Stem Cells Translational Medicine
spellingShingle Berner, Arne, Henkel, Jan, Woodruff, Maria A., Steck, Roland, Nerlich, Michael, Schuetz, Michael A., Hutmacher, Dietmar W., Stem Cells Translational Medicine, Delayed Minimally Invasive Injection of Allogenic Bone Marrow Stromal Cell Sheets Regenerates Large Bone Defects in an Ovine Preclinical Animal Model, Cell Biology, Developmental Biology, General Medicine
title Delayed Minimally Invasive Injection of Allogenic Bone Marrow Stromal Cell Sheets Regenerates Large Bone Defects in an Ovine Preclinical Animal Model
title_full Delayed Minimally Invasive Injection of Allogenic Bone Marrow Stromal Cell Sheets Regenerates Large Bone Defects in an Ovine Preclinical Animal Model
title_fullStr Delayed Minimally Invasive Injection of Allogenic Bone Marrow Stromal Cell Sheets Regenerates Large Bone Defects in an Ovine Preclinical Animal Model
title_full_unstemmed Delayed Minimally Invasive Injection of Allogenic Bone Marrow Stromal Cell Sheets Regenerates Large Bone Defects in an Ovine Preclinical Animal Model
title_short Delayed Minimally Invasive Injection of Allogenic Bone Marrow Stromal Cell Sheets Regenerates Large Bone Defects in an Ovine Preclinical Animal Model
title_sort delayed minimally invasive injection of allogenic bone marrow stromal cell sheets regenerates large bone defects in an ovine preclinical animal model
title_unstemmed Delayed Minimally Invasive Injection of Allogenic Bone Marrow Stromal Cell Sheets Regenerates Large Bone Defects in an Ovine Preclinical Animal Model
topic Cell Biology, Developmental Biology, General Medicine
url http://dx.doi.org/10.5966/sctm.2014-0244