Administration of allogeneic mesenchymal stem cells in lengthening phase accelerates early bone consolidation in rat distraction osteogenesis model

Stem Cell Research & Therapy

Yanhua Yang¹  Weidong Gu¹  Kaijie Zou¹  Yunzhi Peter Yang²  Haixing Wang³  Gang Li³  Xiaoting Zhang³  Sien Lin³  Wayne Yuk Wai Lee³  Qi Pan³  Zhengmeng Yang³  Bo Wei⁴ 

[1] Department of Central Laboratory, Changzhou Seventh People’s Hospital;Department of Orthopaedic Surgery, School of Medicine, Stanford University;Department of Orthopaedic and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong;Orthopaedic Center, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University;

关键词: Distraction osteogenesis;    Mesenchymal stem cells;    Bone consolidation;    Cytokines;   

DOI  :  10.1186/s13287-020-01635-5

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown