Simple SummaryThe importance of stem cells for regenerative medicine has grown significantly in recent years. This is because stem cells can differentiate into multiple cell types and are often easy to recover. Dental pulp stem cells can differentiate into odontoblasts (dentin), osteoblasts, chondrocytes, adipocytes and nerve cells. They are easy to recover and can proliferate, migrate and differentiate in vitro. The regeneration of damaged tissue depends on the homing of the recruited cells and thus on cell migration. However, not all stem cells are equally capable of migrating. Indeed, they may use different modalities, different times or different stimuli. Amoeboid and mesenchymal migration are commonly utilized by mesenchymal stem cells to move, including dental pulp stem cells. Recently, migracytosis and dynamic blebs also appear to be two modalities used by mesenchymal stem cells, although there is still no experimental evidence for their use in dental pulp stem cells. Cells move in response to environmental stimuli interacting with specialized cell receptors. Environmental stimuli can be of a different nature: chemical or physical, including mechanical, which depends on forces that interact with the cells. This review aims to shed light on the characteristics used by dental pulp stem cells to migrate in relation to differentiation options.AbstractHuman dental pulp stem cells (hDPSCs) are adult mesenchymal stem cells (MSCs) obtained from dental pulp and derived from the neural crest. They can differentiate into odontoblasts, osteoblasts, chondrocytes, adipocytes and nerve cells, and they play a role in tissue repair and regeneration. In fact, DPSCs, depending on the microenvironmental signals, can differentiate into odontoblasts and regenerate dentin or, when transplanted, replace/repair damaged neurons. Cell homing depends on recruitment and migration, and it is more effective and safer than cell transplantation. However, the main limitations of cell homing are the poor cell migration of MSCs and the limited information we have on the regulatory mechanism of the direct differentiation of MSCs. Different isolation methods used to recover DPSCs can yield different cell types. To date, most studies on DPSCs use the enzymatic isolation method, which prevents direct observation of cell migration. Instead, the explant method allows for the observation of single cells that can migrate at two different times and, therefore, could have different fates, for example, differentiation and self-renewal. DPSCs use mesenchymal and amoeboid migration modes with the formation of lamellipodia, filopodia and blebs, depending on the biochemical and biophysical signals of the microenvironment. Here, we present current knowledge on the possible intriguing role of cell migration, with particular attention to microenvironmental cues and mechanosensing properties, in the fate of DPSCs.