Scaffold-based delivery of bone marrow mesenchymal stem cell sheet fragments enhances new bone formation in vivo

Publication date: Available online 24 August 2016
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Ge Ma, Jin-Long Zhao, Ming Mao, Jie Chen, Zhi-Wei Dong, Yan-Pu Liu
PurposeStem cell therapy is becoming a potent strategy to shorten the consolidation time and reduce potential complications during distraction osteogenesis. However, the conventional local injection or scaffold-based delivery of bone marrow stem cells (BMSCs) suspension deprive the cells of their endogenous extracellular matrix, which might dampen cell differentiation and tissue regeneration after implantation. Therefore, in our study BMSC cell sheet was established, which was then minced into fragments and loaded onto a hydroxyapatite (HA) scaffold for grafting.MethodsThe purified and characterized BMSCs were grown into a cell sheet, and bone formation and mineralization capacity as well as the cell sheet composition were analyzed. Afterwards, the in vivo osteogenic ability of cell sheet fragments (CSF) was evaluated in immunocompromised mice and rabbit model of distraction osteogenesis (DO).ResultsThe results showed that the BMSC sheet exhibited higher alkaline phosphatase (ALP) activity than osteogenic cell suspension cultures. ALP activity and mineral particles in the cell sheet increased further after osteogenic induction. Moreover, calcium and phosphorus were present only in the osteogenic cell sheet, along with the common elements C, O, Cl, Na and S, as indicated by XPS analysis. In a mouse model, the CSF/HA complex was injected subcutaneously. Micro-CT analysis demonstrated that the osteogenic CSF/HA complex led to a significantly higher bone volume than the BMSC/HA or CSF/HA complexes. The osteogenic CSF/HA specimen showed increased angiogenesis and deposition of collagen I compared to the non-osteogenic CSF/HA or BMSC/HA. Moreover, the osteogenic CSF/HA significantly improved bone consolidation and increased bone mass in DO rabbits.ConclusionCollectively, the incorporation of osteogenic BMSC sheet into HA particles greatly promoted bone regeneration, which offers therapeutic alternatives for distraction osteogenesis.



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