Since stem cell numbers used for regenerative purposes is low in vivo, therapeutic benefits may largely result from cellular interactions including paracrine signaling and direct cell-cell contacts. There is evidence that regenerated tissue is built rather from host tissues than from (trans-) differentiated stem cells, but the latter immensely boost the host tissue cell reactions. Oral hard and connective tissue-derived cells are suspected to react in a unique manner to the presence of stem cells. Thus, we focus on the mutual interplay and synergisms between stem cells and oral tissue cells. The vision is to understand and hence apply the tissue-specific reactions to regenerative therapy strategies.