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Bone marrow CD73(+) mesenchymal stem cells display increased stemness in vitro and promote fracture healing in vivo

Mesenchymal stem cells (MSCs) are multipotent and considered to be of great potential for regenerative medicine. We could show recently (Breitbach, Kimura et al. 2018) that a subpopulation of MSCs as well as sinusoidal endothelial cells (sECs) in the bone marrow (BM) of CD73-EGFP reporter mice could...

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Autores principales: Kimura, Kenichi, Breitbach, Martin, Schildberg, Frank A., Hesse, Michael, Fleischmann, Bernd K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493579/
https://www.ncbi.nlm.nih.gov/pubmed/34632004
http://dx.doi.org/10.1016/j.bonr.2021.101133
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author Kimura, Kenichi
Breitbach, Martin
Schildberg, Frank A.
Hesse, Michael
Fleischmann, Bernd K.
author_facet Kimura, Kenichi
Breitbach, Martin
Schildberg, Frank A.
Hesse, Michael
Fleischmann, Bernd K.
author_sort Kimura, Kenichi
collection PubMed
description Mesenchymal stem cells (MSCs) are multipotent and considered to be of great potential for regenerative medicine. We could show recently (Breitbach, Kimura et al. 2018) that a subpopulation of MSCs as well as sinusoidal endothelial cells (sECs) in the bone marrow (BM) of CD73-EGFP reporter mice could be labeled in vivo. We took advantage of this model to explore the plasticity and osteogenic potential of CD73-EGFP(+) MSCs in vitro and their role in the regenerative response upon bone lesion in vivo. Herein we show that isolated CD73-EGFP(+) MSCs displayed more pronounced stemness and stronger in vitro differentiation capacity into the osteogenic lineage compared to CD73-EGFP(−) MSCs. In a bone fracture model, endogenous BM-resident CD73-EGFP(+) MSCs were found to migrate to the fracture site and differentiate into cartilage and bone cells. Our analysis also showed that CD73-EGFP(+) sECs contributed to the neovascularization of the fracture site. In addition, grafting of CD73-EGFP(+) MSCs into acute bone lesions revealed their capacity to differentiate into chondrocytes and osteocytes in vivo and their contribution to callus formation in the regeneration process of fracture healing. Thus, CD73(+) MSCs display enhanced stemness and osteogenic differentiation potential in vitro and in vivo illustrating a prominent role of the CD73(+) MSC subpopulation to promote fracture repair.
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spelling pubmed-84935792021-10-08 Bone marrow CD73(+) mesenchymal stem cells display increased stemness in vitro and promote fracture healing in vivo Kimura, Kenichi Breitbach, Martin Schildberg, Frank A. Hesse, Michael Fleischmann, Bernd K. Bone Rep Full Length Article Mesenchymal stem cells (MSCs) are multipotent and considered to be of great potential for regenerative medicine. We could show recently (Breitbach, Kimura et al. 2018) that a subpopulation of MSCs as well as sinusoidal endothelial cells (sECs) in the bone marrow (BM) of CD73-EGFP reporter mice could be labeled in vivo. We took advantage of this model to explore the plasticity and osteogenic potential of CD73-EGFP(+) MSCs in vitro and their role in the regenerative response upon bone lesion in vivo. Herein we show that isolated CD73-EGFP(+) MSCs displayed more pronounced stemness and stronger in vitro differentiation capacity into the osteogenic lineage compared to CD73-EGFP(−) MSCs. In a bone fracture model, endogenous BM-resident CD73-EGFP(+) MSCs were found to migrate to the fracture site and differentiate into cartilage and bone cells. Our analysis also showed that CD73-EGFP(+) sECs contributed to the neovascularization of the fracture site. In addition, grafting of CD73-EGFP(+) MSCs into acute bone lesions revealed their capacity to differentiate into chondrocytes and osteocytes in vivo and their contribution to callus formation in the regeneration process of fracture healing. Thus, CD73(+) MSCs display enhanced stemness and osteogenic differentiation potential in vitro and in vivo illustrating a prominent role of the CD73(+) MSC subpopulation to promote fracture repair. Elsevier 2021-09-29 /pmc/articles/PMC8493579/ /pubmed/34632004 http://dx.doi.org/10.1016/j.bonr.2021.101133 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Full Length Article
Kimura, Kenichi
Breitbach, Martin
Schildberg, Frank A.
Hesse, Michael
Fleischmann, Bernd K.
Bone marrow CD73(+) mesenchymal stem cells display increased stemness in vitro and promote fracture healing in vivo
title Bone marrow CD73(+) mesenchymal stem cells display increased stemness in vitro and promote fracture healing in vivo
title_full Bone marrow CD73(+) mesenchymal stem cells display increased stemness in vitro and promote fracture healing in vivo
title_fullStr Bone marrow CD73(+) mesenchymal stem cells display increased stemness in vitro and promote fracture healing in vivo
title_full_unstemmed Bone marrow CD73(+) mesenchymal stem cells display increased stemness in vitro and promote fracture healing in vivo
title_short Bone marrow CD73(+) mesenchymal stem cells display increased stemness in vitro and promote fracture healing in vivo
title_sort bone marrow cd73(+) mesenchymal stem cells display increased stemness in vitro and promote fracture healing in vivo
topic Full Length Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493579/
https://www.ncbi.nlm.nih.gov/pubmed/34632004
http://dx.doi.org/10.1016/j.bonr.2021.101133
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