The Role of Skeletal Stem Cells in the Reconstruction of Bone Defects

Murphy, Matthew P.; Irizarry, Dre; Lopez, Michael; Moore, Alessandra L.; Ransom, Ryan C.; Longaker, Michael T.; Wan, Derrick C.; Chan, Charles K.

doi:10.1097/scs.0000000000003893

Cited by 10 publications

(6 citation statements)

References 100 publications

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“…Consistently with our present data, MSCs implanted in the calvaria, a flat bone exposed to weak mechanical loading, were shown to induce intramembranous bone healing , except when being induced toward a chondrogenic phenotype prior to implantation . In contrast, under the influence of mechanical stimuli, MSCs can differentiate both into osteoblasts and chondrocytes .…”

Section: Discussionsupporting

confidence: 91%

“…The critical‐sized defect in the mouse calvaria requires a considerable amount of bone regeneration, and all three experimental groups demonstrated new bone formation through intramembranous ossification, which is classically observed in this model of bone regeneration . The primings boosted bone formation, collagen extracellular matrix arrangement and, quite remarkably, numerous mineralization nodules were rapidly observed in the FGF‐2 primed defects.…”

Section: Discussionmentioning

confidence: 68%

“…FGF‐2 has been shown to be an osteoblast mitogen and a potent enhancer of bone formation . Along this line, several studies reported the positive effect of local delivery of FGF‐2 on bone healing by stimulating cell proliferation and osteoblastic differentiation . In contrast, FGF‐2 has also been reported to inhibit mineralization induced by MSCs derived from the periodontal ligament in vitro .…”

Section: Discussionmentioning

confidence: 98%

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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

Novais

Lesieur

Sadoine

et al. 2019

Stem Cells Translational Medicine

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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

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

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

Novais

Lesieur

Sadoine

et al. 2019

Stem Cells Translational Medicine

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“…Calvaria are formed by an intramembranous bone process and their defects are expected to heal through the same mechanisms . Remarkably, although being in a microenvironment favoring osteogenic differentiation, that is, a compressed type I collagen scaffold with fibrillary organization mimicking the osteoid matrix , mDPSC cultured in “stem cell conditions” rapidly and directly differentiated in vivo into chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

Mouse Wnt1-CRE-RosaTomato Dental Pulp Stem Cells Directly Contribute to the Calvarial Bone Regeneration Process

et al. 2019

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Stem cells endowed with skeletogenic potentials seeded in specific scaffolds are considered attractive tissue engineering strategies for treating large bone defects. In the context of craniofacial bone, mesenchymal stromal/stem cells derived from the dental pulp (DPSCs) have demonstrated significant osteogenic properties. Their neural crest embryonic origin further makes them a potential accessible therapeutic tool to repair craniofacial bone. The stem cells' direct involvement in the repair process versus a paracrine effect is however still discussed. To clarify this question, we have followed the fate of fluorescent murine DPSCs derived from PN3 Wnt1-CRE-Rosa Tomato mouse molar (T-mDPSCs) during the repair process of calvaria bone defects. Two symmetrical critical defects created on each parietal region were filled with (a) dense collagen scaffolds seeded with T-mDPSCs, (b) noncellularized scaffolds, or (c) no scaffold. Mice were imaged over a 3-month period by microcomputed tomography to evaluate the extent of repair and by biphotonic microscopy to track T-mDPSCs. Histological and immunocytochemical analyses were performed in parallel to characterize the nature of the repaired tissue. We show that T-mDPSCs are present up to 3 months postimplantation in the healing defect and that they rapidly differentiate in chondrocyte-like cells expressing all the expected characteristic markers. T-mDPSCs further maturate into hypertrophic chondrocytes and likely signal to host progenitors that form new bone tissue. This demonstrates that implanted T-mDPSCs are able to survive in the defect microenvironment and to participate directly in repair via an endochondral bone ossification-like process. STEM CELLS 2019;37:701-711 SIGNIFICANCE STATEMENTReconstruction of large bone defects in the craniofacial area poses a continued clinical dilemma. Tissue engineering reconstructive strategies using specific scaffolds combined with stem cells endowed with skeletogenic potentials appear as efficient alternatives. The survival of the cells and their direct participation to new bone formation is, however, still a matter of debate. In this study, implanted cell survival in the defect by using fluorescent dental pulp stem cells and their in vivo tracking by two-photon microscopy was demonstrated. Immunohistochemical analyses further reveal that they directly participate in bone repair through an endochondral ossification process. This study paves the way for a better understanding of the molecular and cellular mechanisms at play during (craniofacial) bone repair before their translation to clinical applications.

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“…Scaffolds can be highly tuned for specific applications that are based on material choice, fabrication method, and surface functionalization [ 192 , 193 ]. Pertinent to craniofacial surgery, synthetic scaffolds can be designed to maintain an undifferentiated stem cell niche for a cranial suture or promote osteogenic differentiation to heal bone defects [ 194 , 195 , 196 , 197 , 198 ]. In the future, surgeons should be able to utilize scaffolds fabricated to control stemness and promote craniofacial growth for improved surgical outcomes, particularly when coupled with appropriate surgical techniques.…”

Section: Development Of Strategies For Treatment and Future Outloomentioning

confidence: 99%

Cranial Neural Crest Cells and Their Role in the Pathogenesis of Craniofacial Anomalies and Coronal Craniosynostosis

Siismets

Hatch

2020

JDB

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Craniofacial anomalies are among the most common of birth defects. The pathogenesis of craniofacial anomalies frequently involves defects in the migration, proliferation, and fate of neural crest cells destined for the craniofacial skeleton. Genetic mutations causing deficient cranial neural crest migration and proliferation can result in Treacher Collins syndrome, Pierre Robin sequence, and cleft palate. Defects in post-migratory neural crest cells can result in pre- or post-ossification defects in the developing craniofacial skeleton and craniosynostosis (premature fusion of cranial bones/cranial sutures). The coronal suture is the most frequently fused suture in craniosynostosis syndromes. It exists as a biological boundary between the neural crest-derived frontal bone and paraxial mesoderm-derived parietal bone. The objective of this review is to frame our current understanding of neural crest cells in craniofacial development, craniofacial anomalies, and the pathogenesis of coronal craniosynostosis. We will also discuss novel approaches for advancing our knowledge and developing prevention and/or treatment strategies for craniofacial tissue regeneration and craniosynostosis.

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The Role of Skeletal Stem Cells in the Reconstruction of Bone Defects

Cited by 10 publications

References 100 publications

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

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

Mouse Wnt1-CRE-RosaTomato Dental Pulp Stem Cells Directly Contribute to the Calvarial Bone Regeneration Process

Cranial Neural Crest Cells and Their Role in the Pathogenesis of Craniofacial Anomalies and Coronal Craniosynostosis

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