It is known that the dental follicle (DF) consists of progenitor cells that give 
rise to the cementum, periodontal ligament, and alveolar bone; but little 
information is available about the regulation of DF cell differentiation into 
either cementogenic or osteogenic cell lineages for the regeneration of diseased 
periodontal tissue. Here, we investigated the roles of DF, Hertwig's epithelial 
root sheath (HERS), and pulp cells in the cementum and during alveolar bone 
formation. We cultured these cells; transplanted them alone or in combination 
into immunocompromised mice; and observed their effects at 6 and 12 weeks. 
Histological and immunohistochemical results revealed that DF cells formed 
cementum-like tissues with immunoreactivity to cementum-derived attached 
protein, bone sialoprotein, type I collagen, and alkaline phosphatase. In 
addition, HERS cells played a role in the induction and maturation of 
cementum-like tissues formed by DF cells. In contrast, implants of DF cells in 
the presence of pulp cells led to the formation of bone-like tissues. 
Interestingly, in the presence of both HERS and pulp cells, DF cells formed both 
cementum-like and bone-like tissues. We demonstrated that while HERS cells are 
able to induce DF cell differentiation into cementoblasts and promote cementum 
formation, pulp cells could direct DF cell differentiation into osteoblasts and 
enhance alveolar bone formation. These results suggest that the combined use of 
DF, HERS, and pulp cells could direct DF cell differentiation into cementoblasts 
and/or osteoblasts in vivo, thus providing a novel strategy for the successful 
repair and regeneration of diseased periodontal tissue.