Recapitulating cranial osteogenesis with neural crest cells in 3-D microenvironments

Namkoong, Bumjin; Güven, Sinan; Ramesan, Shwathy; Liaudanskaya, Volha; Abzhanov, Arhat; Demirci, Utkan

doi:10.1016/j.actbio.2015.12.004

Cited by 10 publications

(10 citation statements)

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“…With respect to mineralized tissue formation, the 4W 2× cell constructs showed the greatest mineralized tissue volume and density, consistent with reports on cell seeding density influencing mesenchymal cell fate (Kim et al 2009; Luo et al 2013; Namkoong et al 2016). Most cells expressed DSPP, OC, or AM—very few expressed both DSPP and OC or DSPP and AM (Appendix Fig.…”

Section: Discussionsupporting

confidence: 88%

Bioengineered Tooth Buds Exhibit Features of Natural Tooth Buds

et al. 2018

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Tooth loss is a significant health issue currently affecting millions of people worldwide. Artificial dental implants, the current gold standard tooth replacement therapy, do not exhibit many properties of natural teeth and can be associated with complications leading to implant failure. Here we propose bioengineered tooth buds as a superior alternative tooth replacement therapy. We describe improved methods to create highly cellularized bioengineered tooth bud constructs that formed hallmark features that resemble natural tooth buds such as the dental epithelial stem cell niche, enamel knot signaling centers, transient amplifying cells, and mineralized dental tissue formation. These constructs were composed of postnatal dental cells encapsulated within a hydrogel material that were implanted subcutaneously into immunocompromised rats. To our knowledge, this is the first report describing the use of postnatal dental cells to create bioengineered tooth buds that exhibit evidence of these features of natural tooth development. We propose future bioengineered tooth buds as a promising, clinically relevant tooth replacement therapy.

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Section: Discussionsupporting

confidence: 88%

Bioengineered Tooth Buds Exhibit Features of Natural Tooth Buds

et al. 2018

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“…Aggrecan expression increases during the endochondral ossification. In line with that, the previous study conducted by Namkoong et al [9] showed that Aggrecan does not show any expression differences between the control and the osteogenic mediums. In this study, the Aggrecan expression increases on the 7 th day in the treatment group with a significant different between group.…”

Section: Discussionsupporting

confidence: 84%

“…The Aggrecan expression is used to evaluate the chondrogenesis for any potential endochondral ossification. In the previous study, the aggrecan expression between MSCs osteogenic culture medium and control medium did not alter significantly different [9] .…”

Section: Introductionmentioning

confidence: 74%

Erken Osteojenik Farklılaşma (In Vitro) Süresince Wistar Sıçanlarda (Rattus novergicus) Gingival Medicinal Signaling Hücrelere Post Trombositten Zengin Fibrin Uygulamasının Agrekan Ekspresyonuna Etkisi

Nugraha¹,

Narmada²,

Ernawati³

et al. 2019

Kafkas Univ Vet Fak Derg

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Platelet Rich Fibrin (PRF) is rich for growth factors which can improve the Gingival Medicinal Signaling Cells' (GMSCs) osteogenic differentiation. Aggrecan is chondrogenic differentiation marker which has a significant role in the early stage of GMSCs' osteogenic differentiation. This study aimed to analyze the expression of Aggrecan post PRF administration on the osteogenic differentiation in vitro. This research is a true experimental study using the post-test only control group design with a simple random sampling. GMSCs were isolated from the lower gingival tissue of healthy male Wistar rats (Rattus novergicus) (n=4), weighted around 250 g, a month old, then cultured for 2 weeks and passaged for 4-5 days. GMSCs in the passage 3-5 were cultured in five M24 plates (N=54; n=6/group) for 7 days, 14 days, and 21 days in three different culture mediums, they were negative control group which included α Modified Eagle Medium; positive control group which contained High Glucose-Dulbecco's Modified Eagle Medium (DMEM-HG) combined with osteogenic medium; and at last, treatment group which were DMEM-HG combined with both osteogenic medium and PRF. A one-way Analysis of Variance (ANOVA) test (P<0.05) was performed. The treatment group showed the highest Aggrecan expression of 16.15±2.15 on the 7 th day. The lowest Aggrecan expression with a value of 3.67±0.76 on the 21 th day occurred in the negative control group. There was a significant difference of Aggrecan expression between groups (P<0.05). PRF administration unexpectedly stimulates Aggrecan expression of GMSCs during the osteogenic differentiation that useful to accelerate the bone remodeling or neo-cartilage formation.

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“…RUNX2 is usually expressed early in the osteogenic differentiation process and regulates the differentiation of MSCs to osteoblasts as well as the expression of other osteogenic genes, such as BSP1 , COLLAGEN1 and OSTEOCALCIN . However, it is downregulated during late stage osteogenesis as RUNX2 is not required for further ossification . A similar trend was seen in OSTERIX expression, another transcription factor essential in initiating osteogenesis, with the eMSCs upregulating it later than BM-MSCs did (Figure B).…”

Section: Resultsmentioning

confidence: 73%

Comparative Craniofacial Bone Regeneration Capacities of Mesenchymal Stem Cells Derived from Human Neural Crest Stem Cells and Bone Marrow

Srinivasan

Teo

Poon

et al. 2020

ACS Biomater. Sci. Eng.

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Most craniofacial bones are derived from the ectodermal germ layer via neural crest stem cells, which are distinct from mesoderm-derived long bones. However, current craniofacial bone tissue engineering approaches do not account for this difference and utilize mesoderm-derived bone marrow mesenchymal stem cells (BM-MSCs) as a paradigm cell source. The effect of the embryonic origin (ontogeny) of an MSC population on its osteogenic differentiation potential and regenerative ability still remains unresolved. To clarify the effects of MSC ontogeny on bone regenerative ability, we directly compared the craniofacial bone regenerative abilities of an ecto-mesenchymal stem cell (eMSC) population, which is derived from human embryonic stem cells via a neural crest intermediate, with mesodermal adult BM-MSCs. eMSCs showed comparable osteogenic and chondrogenic ability to BM-MSCs in 2-D in vitro culture, but lower adipogenic ability. They exhibited greater proliferation than BM-MSCs and comparable construct mineralization in a well-established 3-D polycaprolactone-tricalcium phosphate (PCL-TCP) scaffold system in vitro. eMSC-derived 3D osteogenic constructs were maintained for longer in a proliferative osteoblast state and exhibited differential levels of genes related to fibroblast growth factor (FGF) signaling compared to BM-MSCs. Although both eMSC and BM-MSC-seeded scaffold constructs could promote bone regeneration in a rat calvarial defect model, eMSC-derived osseous constructs had significantly higher cellularity due to increased number of proliferative (Ki67+) cells than those seeded with BM-MSCs, and exhibited enhanced new bone formation in the defect area as compared to untreated controls. Overall, our study demonstrates the potential of human eMSCs for future clinical use in craniofacial regeneration applications and indicates the importance of considering MSC origin when selecting an MSC source for regenerative applications.

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Recapitulating cranial osteogenesis with neural crest cells in 3-D microenvironments

Cited by 10 publications

References 50 publications

Bioengineered Tooth Buds Exhibit Features of Natural Tooth Buds

Bioengineered Tooth Buds Exhibit Features of Natural Tooth Buds

Erken Osteojenik Farklılaşma (In Vitro) Süresince Wistar Sıçanlarda (Rattus novergicus) Gingival Medicinal Signaling Hücrelere Post Trombositten Zengin Fibrin Uygulamasının Agrekan Ekspresyonuna Etkisi

Comparative Craniofacial Bone Regeneration Capacities of Mesenchymal Stem Cells Derived from Human Neural Crest Stem Cells and Bone Marrow

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