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The optimal time to inject bone mesenchymal stem cells for fracture healing in a murine model

BACKGROUND: Bone marrow is an important source of stem cells, which can promote bone fracture healing. METHODS: We investigated the optimal time to inject bone marrow mesenchymal stem cells (BMSCs) in a C57 murine unilateral, transverse, femur fracture model. BMSCs transfected with red fluorescent p...

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Autores principales: Wang, Xin, Wang, Cheng, Gou, Wenlong, Xu, Xiaolong, Wang, Yu, Wang, Aiyuan, Xu, Wenjing, Guo, Quanyi, Liu, Shuyun, Lu, Qiang, Meng, Haoye, Yuan, Mei, Peng, Jiang, Lu, Shibi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202840/
https://www.ncbi.nlm.nih.gov/pubmed/30359311
http://dx.doi.org/10.1186/s13287-018-1034-7
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author Wang, Xin
Wang, Cheng
Gou, Wenlong
Xu, Xiaolong
Wang, Yu
Wang, Aiyuan
Xu, Wenjing
Guo, Quanyi
Liu, Shuyun
Lu, Qiang
Meng, Haoye
Yuan, Mei
Peng, Jiang
Lu, Shibi
author_facet Wang, Xin
Wang, Cheng
Gou, Wenlong
Xu, Xiaolong
Wang, Yu
Wang, Aiyuan
Xu, Wenjing
Guo, Quanyi
Liu, Shuyun
Lu, Qiang
Meng, Haoye
Yuan, Mei
Peng, Jiang
Lu, Shibi
author_sort Wang, Xin
collection PubMed
description BACKGROUND: Bone marrow is an important source of stem cells, which can promote bone fracture healing. METHODS: We investigated the optimal time to inject bone marrow mesenchymal stem cells (BMSCs) in a C57 murine unilateral, transverse, femur fracture model. BMSCs transfected with red fluorescent protein (RFP-BMSCs) were injected via the tail vein on day 1, 7, or 14 post-fracture. AMD3100 (inhibitor of stromal cell-derived factor 1 [SDF-1]) was also injected before RFP-BMSCs in one group for comparison; a control group received saline injections. RFP-BMSC migration and fracture healing were evaluated by in vivo fluorescence assay. Micro-CT was performed and mechanical testing and histological analysis. Chemokine levels were evaluated by quantitative real-time PCR and western blotting. RESULTS: Following injection on day 7 post-fracture, RFP-BMSCs more frequently homed to the fracture site and remained for a longer duration. Bone volume and bone mineral density were increased when BMSCs were injected on day 7 post-fracture (P < 0.05). The mechanical properties of fractured femurs were improved following day-7 BMSC injection. Histology confirmed that BMSC injection improved the formation of new bones. CONCLUSIONS: Chemokines that induce BMSC migration were highly expressed, and protein levels of osteogenesis-related factors were increased. Seven days after fracture may be the optimal time for injection of BMSCs to promote fracture healing. Additionally, the SDF-1/CXCR4 pathway may play an important role in fracture healing following BMSC injection.
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spelling pubmed-62028402018-11-01 The optimal time to inject bone mesenchymal stem cells for fracture healing in a murine model Wang, Xin Wang, Cheng Gou, Wenlong Xu, Xiaolong Wang, Yu Wang, Aiyuan Xu, Wenjing Guo, Quanyi Liu, Shuyun Lu, Qiang Meng, Haoye Yuan, Mei Peng, Jiang Lu, Shibi Stem Cell Res Ther Research BACKGROUND: Bone marrow is an important source of stem cells, which can promote bone fracture healing. METHODS: We investigated the optimal time to inject bone marrow mesenchymal stem cells (BMSCs) in a C57 murine unilateral, transverse, femur fracture model. BMSCs transfected with red fluorescent protein (RFP-BMSCs) were injected via the tail vein on day 1, 7, or 14 post-fracture. AMD3100 (inhibitor of stromal cell-derived factor 1 [SDF-1]) was also injected before RFP-BMSCs in one group for comparison; a control group received saline injections. RFP-BMSC migration and fracture healing were evaluated by in vivo fluorescence assay. Micro-CT was performed and mechanical testing and histological analysis. Chemokine levels were evaluated by quantitative real-time PCR and western blotting. RESULTS: Following injection on day 7 post-fracture, RFP-BMSCs more frequently homed to the fracture site and remained for a longer duration. Bone volume and bone mineral density were increased when BMSCs were injected on day 7 post-fracture (P < 0.05). The mechanical properties of fractured femurs were improved following day-7 BMSC injection. Histology confirmed that BMSC injection improved the formation of new bones. CONCLUSIONS: Chemokines that induce BMSC migration were highly expressed, and protein levels of osteogenesis-related factors were increased. Seven days after fracture may be the optimal time for injection of BMSCs to promote fracture healing. Additionally, the SDF-1/CXCR4 pathway may play an important role in fracture healing following BMSC injection. BioMed Central 2018-10-25 /pmc/articles/PMC6202840/ /pubmed/30359311 http://dx.doi.org/10.1186/s13287-018-1034-7 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Wang, Xin
Wang, Cheng
Gou, Wenlong
Xu, Xiaolong
Wang, Yu
Wang, Aiyuan
Xu, Wenjing
Guo, Quanyi
Liu, Shuyun
Lu, Qiang
Meng, Haoye
Yuan, Mei
Peng, Jiang
Lu, Shibi
The optimal time to inject bone mesenchymal stem cells for fracture healing in a murine model
title The optimal time to inject bone mesenchymal stem cells for fracture healing in a murine model
title_full The optimal time to inject bone mesenchymal stem cells for fracture healing in a murine model
title_fullStr The optimal time to inject bone mesenchymal stem cells for fracture healing in a murine model
title_full_unstemmed The optimal time to inject bone mesenchymal stem cells for fracture healing in a murine model
title_short The optimal time to inject bone mesenchymal stem cells for fracture healing in a murine model
title_sort optimal time to inject bone mesenchymal stem cells for fracture healing in a murine model
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202840/
https://www.ncbi.nlm.nih.gov/pubmed/30359311
http://dx.doi.org/10.1186/s13287-018-1034-7
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