Abstract
Background. Fibrin sealant has been used as a scaffold to deliver genetically modified human muscle-derived stem cells (hMDSCs) for bone regeneration. Alternatively, autologous blood clots are safe, economic scaffolds. This study compared autologous blood clot (BC) with fibrin sealant (FS) as a scaffold to deliver lenti-BMP2/GFP-transduced hMDSCs for bone regeneration. Methods. In vitro osteogenic differentiation was performed using 3D pellet culture and evaluated using microCT and Von Kossa staining. The lenti-GFP transduced cells were then mixed with human blood for evaluation of osteogenic differentiation. Furthermore, a murine critical- sized calvarial defect model was utilized to compare BC and FS scaffolds for lenti-BMP2/GFP-transduced hMDSCs mediated bone regeneration and evaluated with micro-CT and histology. Results. Lenti-BMP2/GFP transduced hMDSCs formed significantly larger mineralized pellets than non-transduced hMDSCs. hMDSCs within the human blood clot migrated out and differentiated into ALP+ osteoblasts. In vivo, BC resulted in significantly less new bone formation within a critical-sized calvarial bone defect than FS scaffold, despite no difference observed for GFP+ donor cells, osteoclasts, and osteoblasts in the newly formed bone. Conclusions. Human lenti-BMP2/GFP-transduced hMDSCs can efficiently undergo osteogenic differentiation in vitro. Unexpectedly, the newly regenerated bone in BC group was significantly less than the FS group. The autologous blood clot scaffold is less efficacious for delivering stem cells for bone regeneration than fibrin sealant.
Highlights
The results demonstrated that fibrin sealant (Tisseel, Baxter)-mediated bone regeneration led to a bone tissue quality comparable to native bone [11]
This study demonstrates that lenti-bone morphogenetic protein-2 (BMP2)/GFP human muscle-derived stem cells (hMDSCs) undergo osteogenic differentiation more extensively than non-transduced hMDSCs
Our results indicated that blood clot delivery of lenti-BMP2/GFPtransduced hMDSCs resulted in significantly lower amounts of new bone formation within a critical-sized calvarial defect compared to the fibrin sealant
Summary
Bone tissue engineering mimics bone healing by providing bone morphogenic proteins, stem cells and a supportive or bioactive scaffold. Many osteo-inductive scaffolds, such as demineralized bone matrix, biphasic calcium phosphate [1,2,3,4,5], tricalcium phosphate (TCP) [6,7], hydroxyapatite [8], and collagen sponge or gel [9,10], have been used as supportive materials for bone regeneration. Previous work by our group compared different scaffolds for the use of delivery of muscle derived stem cell-mediated bone regeneration. Fibrin sealant has been used as a scaffold to deliver genetically modified human muscle-derived stem cells (hMDSCs) for bone regeneration. Autologous blood clots are safe, economic scaffolds. This study compared autologous blood clot (BC) with fibrin sealant (FS) as a scaffold to deliver lenti-BMP2/GFP-transduced hMDSCs for bone regeneration
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
