gms | German Medical Science

Objectives: Sufficient bone regeneration is a prerequisite for the treatment of critical bone defects or fractures. While bone marrow stem cells (BM-MSC) are used since many years in bone tissue engineering applications, dental pulp stem cells (DPSC) were identified at first in 2001. DPSC are readily accessible, occur in high amounts and show a high proliferation and differentiation capability. The aim of this in-vivo study was to investigate the bone regenerative potential of DPSC in comparison to BM-MSC in a murine critical size bone defect.

Methods: This study was performed on twenty-four 12-weeks-old male nu/nu nude mice that were randomized into two groups: DPSC and BM-MSC group. Therefore, mineralized collagen matrix scaffolds were seeded with 5x10^4 human DPSC or human BM-MSC of four different healthy donors.

Critical size bone defects of 2 mm length were created at the right femur of each mouse and stabilized by an external fixator. After six weeks animals were euthanized and microcomputed tomography scans were done. For histomorphological investigations, hematoxylin and eosin staining was performed. The degree of healing of the defect was evaluated by three independent observers on three representative sections per animal according to Huo et al., using a scale ranging from fibrous tissue only (grade 0) to woven bone (grade 10). Descriptive statistics included means and standard deviations. Unpaired t-test was used for statistical analysis between the groups. Differences were considered significant when p<0.05.

Results and conclusion: All mice survived the 6-week observation period. µCT evaluation of the BV at the defect site after a 6-week follow-up showed significantly higher bone volume when DPSC were implanted at the defect side (DPSC vs. BM-MSC; 4.6 ± 3.1 mm³ vs. 3.1 ± 0.8 mm³, p=0.0497). No intergroup difference was found for BMD (DPSC vs. BM-MSC; 825 ± 64 mgHA/cm³ vs. 811 ± 91 mgHA/cm³, p=0.6558). Histological analysis for the degree of healing of the defect showed a significantly higher score of defect healing for the DPSC group (DPSC vs. BM-MSC; 6.8 ± 1.6 vs. 6.0 ± 1.5, p=0.0003). To our knowledge, this is the first study in a femoral critical size bone defect model showing, that native human DPSC are able to produce a significantly higher amount of bone volume and degree of defect healing, in comparison to native human BM-MSC, while BMD was equal. Since DPSC are easily available for example from extraction of third molar tooth and can be preserved by cryoconservation, these cells are a promising source for future biological concepts of bone regeneration.

Our study demonstrated in a critical size femoral bone defect model, that DPSC significantly improve bone regeneration and degree of defect healing compared with BM-MSC.