Predifferentiated Gingival Stem Cell-Induced Bone Regeneration in Rat Alveolar Bone Defect Model.

ABSTRACT

Cleft alveolus, a common birth defect of the maxillary bone, affects one in 700 live births every year. This defect is traditionally restored by autogenous bone grafts or allografts, which may possibly cause complications. Cell-based therapies using the mesenchymal stem cells (MSCs) derived from human gingiva (gingiva-derived mesenchymal stem cells [GMSCs]) is attracting the research interest due to their highly proliferative and multilineage differentiation capacity. Undifferentiated GMSCs expressed high level of MSC-distinctive surface antigens, including CD73, CD105, CD90, and CD166. Importantly, GMSCs induced with osteogenic medium for a week increased the surface markers of osteogenic phenotypes, such as CD10, CD92, and CD140b, indicating their osteogenic potential. The objective of this study was to assess the bone regenerative efficacy of predifferentiated GMSCs (dGMSCs) toward an osteogenic lineage in combination with a self-assembling hydrogel scaffold PuraMatrix™ (PM) and/or bone morphogenetic protein 2 (BMP2), on a rodent model of maxillary alveolar bone defect. A critical size maxillary alveolar defect of 7 mm × 1 mm × 1 mm was surgically created in athymic nude rats. The defect was filled with either PM/BMP2 or PM/dGMSCs or the combination of three (PM/dGMSCs/BMP2) and the bone regeneration was evaluated at 4 and 8 weeks postsurgery. New bone formation was evaluated by microcomputed tomography and histology using Hematoxylin and Eosin staining. The results demonstrated the absence of spontaneous bone healing, either at 4 or 8 weeks postsurgery in the defect group. However, the PM/dGMSCs/BMP2 group showed significant enhancement in bone regeneration at 4 and 8 weeks postsurgery, compared with the transplantation of individual material/cells alone. Apart from developing the smallest critical size defect, results showed that PM/dGMSCs/BMP2 could serve as a promising option for the regeneration of bone in the cranio/maxillofacial region in humans.