METHODS: (1) Immunohistochemical analysis of the cell proliferation zones 24-48h after pulp exposure. (2) Histological analysis of dentin formation after implantation of pulp-derived clonal precursor cells in the rat molar. RESULTS: We have identified three well-delimited zones of cell proliferation 24-48h after pulp exposure. In the crown, cells leaving their quiescent state are recruited in the isthmus between the mesial and central parts of the pulp chamber as well as between the coronal pulp and the upper pulp part of the root. The restricted location of these mitotic cells within the crown precisely overlaps the area where the dentinal bridge will be formed. In the root, far from the inflammatory site, proliferative cells can also be visualized near the apex. Besides, by exploiting a mouse pulp-derived cell line, we provide the prime evidence that implantation of exogenous stem cells in a rat molar leads to the formation of a robust dentin barrier. Osteodentin totally fills the mesial pulp chamber and in turn, protects the residual pulp. The pulp vitality is preserved and the inflammatory process is also rapidly resolved. Thus, a pulp-derived stem cell line has the ability to contribute to heal a wounded pulp when re-introduced within its “natural” environment. These data provide the foundation for characterizing the signals that support their reparative activity. CONCLUSIONS: Future prospects will aim to determine whether the implanted pulpal cells are directly involved in reparative dentin formation or whether they induce the recruitment and differentiation of host progenitor cells. Our pre-clinical experimental approach paves the way to the development of cellular therapies for pulp injury.