Priming Dental Pulp Stem Cells from Human Exfoliated Deciduous Teeth with Fibroblast Growth Factor-2 Enhances Mineralization Within Tissue-Engineered Constructs Implanted in Craniofacial Bone Defects

Abstract

The craniofacial area is prone to trauma or pathologies often resulting in large bone damages. One potential treatment option is the grafting of a tissue‐engineered construct seeded with adult mesenchymal stem cells (MSCs). The dental pulp appears as a relevant source of MSCs, as dental pulp stem cells display strong osteogenic properties and are efficient at bone formation and repair. Fibroblast growth factor‐2 (FGF‐2) and/or hypoxia primings were shown to boost the angiogenesis potential of dental pulp stem cells from human exfoliated deciduous teeth (SHED). Based on these findings, we hypothesized here that these primings would also improve bone formation in the context of craniofacial bone repair. We found that both hypoxic and FGF‐2 primings enhanced SHED proliferation and osteogenic differentiation into plastically compressed collagen hydrogels, with a much stronger effect observed with the FGF‐2 priming. After implantation in immunodeficient mice, the tissue‐engineered constructs seeded with FGF‐2 primed SHED mediated faster intramembranous bone formation into critical size calvarial defects than the other groups (no priming and hypoxia priming). The results of this study highlight the interest of FGF‐2 priming in tissue engineering for craniofacial bone repair. Stem Cells Translational Medicine 2019;8:844&857

Therapeutic Properties of Mesenchymal Stromal/Stem Cells: The Need of Cell Priming for Cell-Free Therapies in Regenerative Medicine

“…In particular, TNF-α preconditioning stimulated MSCs to increase Wnt3a levels in the EXOs that, in turn, further improved cell proliferation and bone differentiation when compared to CM from unconditioned MSCs [ 64 ]. Regenerative properties of MSCs on bone were also shown by Novais et al who demonstrated that both basic fibroblast growth factor (bFGF) and hypoxic priming improved MSCs proliferation and osteogenic differentiation resulting in the repair of critical size calvarial bone defects created in nude mice [ 65 ].…”

Stem Cells Regenerating the Craniofacial Skeleton: Current State-Of-The-Art and Future Directions

“…The unique secretome profile of SHEDs shows modulatory activity during differentiation in osteogenic lineages, leading to an increase in neoangiogenesis [ 32 ]. Additionally, SHEDs have been shown to effectively form new calvarial bone in a critical-size defect experiment, with greater capacity compared to other odontogenic tissue-derived cell lines in an FGF-2-primed collagenous hydrogel deprived of oxygen, ultimately demonstrating significantly increased intramembranous ossification capacity [ 33 ].…”

Extracellular Matrix Composition and Remodeling: Current Perspectives on Secondary Palate Formation, Cleft Lip/Palate, and Palatal Reconstruction

“…Concerning bone repair, SHEDs are better for forming new bone in a calvaria critical-size defect model, when compared to other dental MSCs and BMSCs. Recently, human SHEDs seeded onto dense collagen hydrogels, which were primed with FGF-2 and submitted to hypoxia conditions before implantation, improved intramembranous bone formation in an immunodeficient calvaria critical-size bone defect mouse model (Novais et al, 2019). Most of the 56 articles thoroughly analyzed in a systematic review reported good results and the relevance of human DPSCs for bone engineering in animal models or human clinical treatments (Leyendecker Junior et al, 2018).…”