Deciduous Dental Pulp Stem Cells for Maxillary Alveolar Reconstruction in Cleft Lip and Palate Patients

Daniela Y S Tanikawa, Carla C G Pinheiro, Maria Cristina A Almeida, Claudia R G C M Oliveira, Renata de Almeida Coudry, Diógenes Laercio Rocha, Daniela Franco Bueno, Daniela Y S Tanikawa, Carla C G Pinheiro, Maria Cristina A Almeida, Claudia R G C M Oliveira, Renata de Almeida Coudry, Diógenes Laercio Rocha, Daniela Franco Bueno

Abstract

Background: To reduce morbidity to cleft patients, new approaches have been developed and here, we report for the first time the use of deciduous dental pulp stem cells (DDPSC) associated with a hydroxyapatite-collagen sponge (Bio-Oss Collagen® 250 mg, Geistlich) for closing alveolar defects during secondary dental eruption, further comparing these results to historical controls.

Methods: Six patients, aged 8 to 12, were selected. Autologous DDPSC were isolated from each patient, then associated with the biomaterial and this bone tissue engineered set was used to fill the alveolar defect. Computed tomography was performed to assess both preoperative and 6- and 12-month postoperative outcomes. Overall morbidity was recorded. Historical controls consisted of sixteen patients previously selected and randomly assigned to group one (rhBMP-2) or group two (iliac crest bone graft).

Results: DDPSC could be isolated and characterized as mesenchymal stem cells. Progressive alveolar bone union has occurred in all patients. Similarly to group two 75.4%, SD ± 4.0, p > 0.999, but statistically different from group one (59.6%, SD ± 9.9, p > 0.999, but statistically different from group one (59.6%, SD ± 9.9.

Conclusion: For this selected group of patients, DDPSC therapy resulted in satisfactory bone healing with excellent feasibility and safety, which adds significantly to the prospect of stem cell use in clinical settings. Clinical Question/Level of Evidence. Therapeutic, II. This trial is registered with https://ichgcp.net/clinical-trials-registry/NCT01932164?term=NCT01932164&rank=1.

Conflict of interest statement

The authors declare that they have no competing interests.

Copyright © 2020 Daniela Y. S. Tanikawa et al.

Figures

Figure 1
Figure 1
Representative strategy for autologous bone tissue engineering using DDPSC.
Figure 2
Figure 2
Multilineage differentiation “in vitro”. (a) The control group of DDPSC chondrogenic differentiation. (b) Chondrogenic differentiation after three weeks of DDPSC induction stained with Alcian Blue; black arrows show the extracellular matrix formation—mucopolysaccharides. (c) The control group of DDPSC osteogenic differentiation. (d) Osteogenic differentiation after three weeks of DPSC induction stained with Alizarin Red S; the black arrows show the calcium nodules. (e) Control group of DDPSC. (f) Adipocytes stained with Oil Red obtained after the adipogenic induction of DPSC during 18 days; black arrows show the fat vesicles. All the scale bars represent 100 μm.
Figure 3
Figure 3
Electron microscopy. Scaffold 250 mg Bio-Oss Collagen® (Geistlich Biomaterials AG, Wolhusen, Germany) seeded with DDPSC; yellow arrows show DDPSC, and white arrows show the scaffold (Bio-Oss®).
Figure 4
Figure 4
Patient that has received alveolar bone tissue engineering graft (DDPSC associated with 250 mg Bio-Oss Collagen®). Computed tomography images of the same patient showing the alveolar cleft fill by bone 6 and 12 months after the use of bone tissue engineering strategies (DDPSC associated with Bio-Oss Collagen®) and the canine tooth eruption after 12 months. (a) Preoperative—presence of alveolar cleft; (b) 6 months postoperatively—the alveolar cleft filled by new bone, and (c) 12 months postoperatively—canine tooth eruption in the new bone formed using the DDPSC associated with Bio-Oss Collagen®.
Figure 5
Figure 5
Analysis of volumetric and bone filling. (a) Volumetric representative graph. (b) Bone filling representative graph.
Figure 6
Figure 6
Histology of the bone formed with DDPSC associated with Bio-Oss Collagen® after 12 months. Histology of the bone formed after 12 months of the use of bone tissue engineering strategy (DDPSC associated with Bio-Oss Collagen® (Geitlish) to close the alveolar bone cleft of cleft lip and palate patients. The scale bars represent 200 μm. The yellow arrow shows the presence of young bone (Haversian canal), and the black arrows show the presence of remaining biomaterial (Bio-Oss Collagen®, Geitlish) that was not reabsorbed in twelve months.

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