A historical perspective on the discovery of human dental follicle cells for regenerative dentistry

Objectives This narrative review aims to summarize and contextualize more than two decades of research on human dental follicle cells (DFCs), focusing on their biological characteristics, regenerative capacity, and potential applications in dentistry and immunotherapy. Design Articles were selected based on the literature of non-human propedeutics since the 1990s and human DFC research since its inception in 2005. The focus was set on the isolation, characterization, cultivation, and therapeutic prospects of DFCs as progenitor cells derived from the mesodermal tooth germ. Results DFCs exhibit multipotent differentiation potential and pronounced immunomodulatory properties. Their developmental origin not only provides specific insights into the cellular processes underlying tooth formation and the regeneration of dental tissue, but also opens up perspectives for novel therapies in dentistry, such as the formation of a biological tooth root. Conclusions The findings highlight the potential of DFCs for regenerative dentistry and immunotherapies in general, and provide a solid basis for future work in these research areas.