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Osteogenic Potential of Nager Syndrome Dental Pulp Stem Cells

Yuan, Joyce T; Bueno, Daniela F; Zuk, Patricia; Tabit, Christina J; Bradley, James P
David Geffen School of Medicine at UCLA
2012-02-14

Presenter: Joyce T Yuan

Affidavit:
I certify that medical student Joyce T Yuan did a majority of the basic science research with regards to the osteogenic potential of Nager syndrome dental pulp stem cells.

Director Name: James P Bradley

Author Category: Student
Presentation Category: Basic Science Research
Abstract Category: Craniomaxillofacial

How does this presentation meet the established conference educational objectives?
Conference participants will learn about advances in therapy for patients with congenital craniofacial deformities, specifically Nager syndrome patients, using a non-invasive source of mesenchymal stem cells. Participants will learn about how surgery morbidity for Nager syndrome patients may be decreased by pre-induced dental pulp stem cells. We will discuss a microdistraction model designed by our group to exert linear forces on cells, mimicking distraction osteogenesis for research purposes and for possible therapy in the future. The presentation will address how the exploration of Nager syndrome pathology in basic science research can allow for improved patient counseling and therapy for Nager syndrome.

How will your presentation be used by practicing physicians in the audience?
Physicians will learn that dental pulp stem cells from exfoliated deciduous teeth are a promising non-invasive source of stem cells that may be used for therapy for Nager syndrome and craniofacial disorders. They will learn of our recent research approaches, and can use information from the proposed presentation to conduct research, develop therapy, and counsel patients with Nager syndrome.

PURPOSE: Nager syndrome patients with craniofacial and limb deformities require bone reconstruction. Novel stem cell therapies may be used to decrease donor site morbidity. We characterized dental pulp stem cells of Nager syndrome patients, focusing on osteogenic potential and functional changes in a microdistractor model.

METHODS: Dental pulp stem cells (DPSCs) were isolated from deciduous teeth in Nager and normal patients. Mesenchymal origin was confirmed by flow cytometry. Osteogenesis of DPSCs grown in osteogenic media was confirmed by von Kossa and rt-PCR (runx2, alkaline phosphatase, osteocalcin, osteonectin and osteopontin). DPSCs were stressed in an in vitro microdistraction model; effect on osteogenesis was quantified with rt-PCR.

RESULTS: Nager DPSCs were positive for CD29 and CD90 while negative for CD105, CD34, and CD31. Nager DPSCs showed positive von Kossa staining and rt-PCR results: Runx2 (2.3 fold at day 21), alkaline phosphatase (large increase at day 14 vs negligible baseline), osteonectin (9.1 fold at day 7), osteocalcin (increase at day 7 vs negligible baseline). Nager DPSCs exposed to microdistraction vs. unstressed condition: Runx2 (6.2 fold at day 7), alkaline phosphatase (0.2 fold at day 4), osteonectin (17.6 fold at day 4), osteopontin (43.6 fold at day 1), osteocalcin (0.05 fold at day 7).

CONCLUSIONS: Mesenchymal cells from dental pulp of Nager syndrome patients have osteogenic potential. Understanding of signaling during osteogenesis in Nager syndrome can be used to reduce morbidity during bone reconstruction. Exfoliated deciduous teeth are a promising non-invasive source of stem cells for therapy in Nager syndrome patients.

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