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Regenerative endodontics is evolving rapidly as an alternative to conventional root canal therapy, aiming not merely to disinfect and fill root canals, but to restore viable pulp tissue with physiological functions such as immune defense, innervation, and dentinogenesis. Central to this paradigm are stem cell–based therapies, which, in concert with scaffolds and signaling factors, offer potential to regenerate the pulp–dentin complex in teeth with necrotic or damaged pulps. This review summarizes the latest progress in the field, focusing on (1) sources of stem cells (e.g. dental pulp stem cells, stem cells from the apical papilla, mesenchymal stem cells of non dental origin, and induced pluripotent stem cells), (2) scaffold design and biomaterial strategies, (3) delivery of growth factors and bioactive cues, (4) cell transplantation vs. cell homing approaches, (5) in vitro, in vivo, and early clinical evidence, and (6) major challenges and future directions. Evidence from animal studies and limited human trials shows promise in root maturation, vascularization, and functional tissue formation. However, full regeneration of the native pulp–dentin architecture — particularly with true odontoblast layer, innervation, and predictable function — remains elusive. Key hurdles include controlling stem cell differentiation and proliferation, immune compatibility, standardized protocols, safety (e.g. tumorigenesis risk), and regulatory issues. Emerging innovations such as cell-free secretomes or exosomes, 3D bioprinting of scaffolds, gene engineering for guided differentiation, and smart biomaterials responsive to microenvironment cues may help overcome current limitations. To accelerate translation toward routine clinical use, rigorous multicenter trials with long-term follow-up, development of GMP grade cell banks, and interdisciplinary collaboration are essential.

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