Administration of allogeneic mesenchymal stem cells in lengthening phase accelerates early bone consolidation in rat distraction osteogenesis model
Abstract Background Distraction osteogenesis (DO) is a surgical technique to promote bone regeneration which may require long duration for bone consolidation. Bone marrow-derived mesenchymal stem cells (MSCs) have been applied to accelerate bone formation in DO. However, the optimal time point for c...
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| Format: | Article |
| Language: | English |
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BMC
2020-03-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | http://link.springer.com/article/10.1186/s13287-020-01635-5 |
| _version_ | 1818891129763921920 |
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| author | Yanhua Yang Qi Pan Kaijie Zou Haixing Wang Xiaoting Zhang Zhengmeng Yang Wayne Yuk Wai Lee Bo Wei Weidong Gu Yunzhi Peter Yang Sien Lin Gang Li |
| author_facet | Yanhua Yang Qi Pan Kaijie Zou Haixing Wang Xiaoting Zhang Zhengmeng Yang Wayne Yuk Wai Lee Bo Wei Weidong Gu Yunzhi Peter Yang Sien Lin Gang Li |
| author_sort | Yanhua Yang |
| collection | DOAJ |
| description | Abstract Background Distraction osteogenesis (DO) is a surgical technique to promote bone regeneration which may require long duration for bone consolidation. Bone marrow-derived mesenchymal stem cells (MSCs) have been applied to accelerate bone formation in DO. However, the optimal time point for cell therapy in DO remains unknown. This study sought to determine the optimal time point of cell administration to achieve early bone consolidation in DO. We hypothesized that the ratio of circulating MSCs to peripheral mononuclear cells and the level of cytokines in serum might be indicators for cell administration in DO. Methods Unilateral tibial osteotomy with an external fixator was performed in adult Sprague Dawley rats. Three days after osteotomy, the tibia was lengthened at 0.5 mm/12 h for 5 days. At first, 5 rats were used to analyze the blood components at 6 different time points (3 days before lengthening, on the day lengthening began, or 3, 6, 10, or 14 days after lengthening began) by sorting circulating MSCs and measuring serum levels of stromal cell-derived factor 1 (SDF-1) and interleukin 1β. Then, 40 rats were used for cell therapy study. A single dose of 5 × 105 allogeneic MSCs was locally injected at the lengthening site on day 3, 6, or 10 after lengthening began, or 3 doses of MSCs were injected at the three time points. Sequential X-ray radiographs were taken weekly. Endpoint examinations included micro-computed tomography analysis, mechanical testing, histomorphometry, and histology. Results The number of circulating MSCs and serum level of SDF-1 were significantly increased during lengthening, and then decreased afterwards. Single injection of MSCs during lengthening phase (on day 3, but not day 6 or 10) significantly increased bone volume fraction, mechanical maximum loading, and bone mineralization of the regenerate. Triple injections of MSCs at three time points also significantly increased bone volume and maximum loading of the regenerates. Conclusion This study demonstrated that bone consolidation could be accelerated by a single injection of MSCs during lengthening when the ratio of peripheral MSCs to mononuclear cells and the serum SDF-1 presented at peak levels concurrently, suggesting that day 3 after lengthening began may be the optimal time point for cell therapy to promote early bone consolidation. |
| first_indexed | 2024-12-19T17:35:54Z |
| format | Article |
| id | doaj.art-c237b34cf1a3478e9b30f1ca7f6f858e |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-19T17:35:54Z |
| publishDate | 2020-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-c237b34cf1a3478e9b30f1ca7f6f858e2022-12-21T20:12:20ZengBMCStem Cell Research & Therapy1757-65122020-03-0111111210.1186/s13287-020-01635-5Administration of allogeneic mesenchymal stem cells in lengthening phase accelerates early bone consolidation in rat distraction osteogenesis modelYanhua Yang0Qi Pan1Kaijie Zou2Haixing Wang3Xiaoting Zhang4Zhengmeng Yang5Wayne Yuk Wai Lee6Bo Wei7Weidong Gu8Yunzhi Peter Yang9Sien Lin10Gang Li11Department of Central Laboratory, Changzhou Seventh People’s HospitalDepartment of Orthopaedic and Traumatology, Faculty of Medicine, The Chinese University of Hong KongDepartment of Central Laboratory, Changzhou Seventh People’s HospitalDepartment of Orthopaedic and Traumatology, Faculty of Medicine, The Chinese University of Hong KongDepartment of Orthopaedic and Traumatology, Faculty of Medicine, The Chinese University of Hong KongDepartment of Orthopaedic and Traumatology, Faculty of Medicine, The Chinese University of Hong KongDepartment of Orthopaedic and Traumatology, Faculty of Medicine, The Chinese University of Hong KongOrthopaedic Center, Affiliated Hospital of Guangdong Medical University, Guangdong Medical UniversityDepartment of Central Laboratory, Changzhou Seventh People’s HospitalDepartment of Orthopaedic Surgery, School of Medicine, Stanford UniversityDepartment of Orthopaedic and Traumatology, Faculty of Medicine, The Chinese University of Hong KongDepartment of Orthopaedic and Traumatology, Faculty of Medicine, The Chinese University of Hong KongAbstract Background Distraction osteogenesis (DO) is a surgical technique to promote bone regeneration which may require long duration for bone consolidation. Bone marrow-derived mesenchymal stem cells (MSCs) have been applied to accelerate bone formation in DO. However, the optimal time point for cell therapy in DO remains unknown. This study sought to determine the optimal time point of cell administration to achieve early bone consolidation in DO. We hypothesized that the ratio of circulating MSCs to peripheral mononuclear cells and the level of cytokines in serum might be indicators for cell administration in DO. Methods Unilateral tibial osteotomy with an external fixator was performed in adult Sprague Dawley rats. Three days after osteotomy, the tibia was lengthened at 0.5 mm/12 h for 5 days. At first, 5 rats were used to analyze the blood components at 6 different time points (3 days before lengthening, on the day lengthening began, or 3, 6, 10, or 14 days after lengthening began) by sorting circulating MSCs and measuring serum levels of stromal cell-derived factor 1 (SDF-1) and interleukin 1β. Then, 40 rats were used for cell therapy study. A single dose of 5 × 105 allogeneic MSCs was locally injected at the lengthening site on day 3, 6, or 10 after lengthening began, or 3 doses of MSCs were injected at the three time points. Sequential X-ray radiographs were taken weekly. Endpoint examinations included micro-computed tomography analysis, mechanical testing, histomorphometry, and histology. Results The number of circulating MSCs and serum level of SDF-1 were significantly increased during lengthening, and then decreased afterwards. Single injection of MSCs during lengthening phase (on day 3, but not day 6 or 10) significantly increased bone volume fraction, mechanical maximum loading, and bone mineralization of the regenerate. Triple injections of MSCs at three time points also significantly increased bone volume and maximum loading of the regenerates. Conclusion This study demonstrated that bone consolidation could be accelerated by a single injection of MSCs during lengthening when the ratio of peripheral MSCs to mononuclear cells and the serum SDF-1 presented at peak levels concurrently, suggesting that day 3 after lengthening began may be the optimal time point for cell therapy to promote early bone consolidation.http://link.springer.com/article/10.1186/s13287-020-01635-5Distraction osteogenesisMesenchymal stem cellsBone consolidationCytokines |
| spellingShingle | Yanhua Yang Qi Pan Kaijie Zou Haixing Wang Xiaoting Zhang Zhengmeng Yang Wayne Yuk Wai Lee Bo Wei Weidong Gu Yunzhi Peter Yang Sien Lin Gang Li Administration of allogeneic mesenchymal stem cells in lengthening phase accelerates early bone consolidation in rat distraction osteogenesis model Stem Cell Research & Therapy Distraction osteogenesis Mesenchymal stem cells Bone consolidation Cytokines |
| title | Administration of allogeneic mesenchymal stem cells in lengthening phase accelerates early bone consolidation in rat distraction osteogenesis model |
| title_full | Administration of allogeneic mesenchymal stem cells in lengthening phase accelerates early bone consolidation in rat distraction osteogenesis model |
| title_fullStr | Administration of allogeneic mesenchymal stem cells in lengthening phase accelerates early bone consolidation in rat distraction osteogenesis model |
| title_full_unstemmed | Administration of allogeneic mesenchymal stem cells in lengthening phase accelerates early bone consolidation in rat distraction osteogenesis model |
| title_short | Administration of allogeneic mesenchymal stem cells in lengthening phase accelerates early bone consolidation in rat distraction osteogenesis model |
| title_sort | administration of allogeneic mesenchymal stem cells in lengthening phase accelerates early bone consolidation in rat distraction osteogenesis model |
| topic | Distraction osteogenesis Mesenchymal stem cells Bone consolidation Cytokines |
| url | http://link.springer.com/article/10.1186/s13287-020-01635-5 |
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