This study reports the successful regeneration of functional teeth in swine using mesenchymal stem cells (MSCs) isolated from the root apical papilla (SCAP). The researchers transplanted both human SCAP and periodontal ligament stem cells (PDLCs) into a minipig model to generate a root/periodontal complex capable of supporting a porcelain crown, resulting in normal tooth function. The study integrates a stem cell-mediated tissue regeneration strategy, engineered materials for structure, and current dental crown technologies. Key findings include the identification of SCAP as a unique population of postnatal stem cells with high proliferation and differentiation potential, superior tissue regeneration capacity compared to dental pulp stem cells (DPSCs), and the ability to form dentin and cementum in immunocompromised mice. In vivo, the combined use of SCAP and PDLCs led to the regeneration of a functional root/periodontal structure, which supported the installation of a porcelain crown. The newly formed bio-roots demonstrated significantly improved compressive strength compared to the original HA/TCP carriers. This hybrid tissue engineering approach holds promise for the regeneration of functional teeth in humans.This study reports the successful regeneration of functional teeth in swine using mesenchymal stem cells (MSCs) isolated from the root apical papilla (SCAP). The researchers transplanted both human SCAP and periodontal ligament stem cells (PDLCs) into a minipig model to generate a root/periodontal complex capable of supporting a porcelain crown, resulting in normal tooth function. The study integrates a stem cell-mediated tissue regeneration strategy, engineered materials for structure, and current dental crown technologies. Key findings include the identification of SCAP as a unique population of postnatal stem cells with high proliferation and differentiation potential, superior tissue regeneration capacity compared to dental pulp stem cells (DPSCs), and the ability to form dentin and cementum in immunocompromised mice. In vivo, the combined use of SCAP and PDLCs led to the regeneration of a functional root/periodontal structure, which supported the installation of a porcelain crown. The newly formed bio-roots demonstrated significantly improved compressive strength compared to the original HA/TCP carriers. This hybrid tissue engineering approach holds promise for the regeneration of functional teeth in humans.