Journal of Dentistry · Oct 28, 2026

SHED in Regenerative Medicine: Cell-Based Therapies and Cell-Free Strategies

By Liu Y, Huang M, Dissanayaka WL et al.

INTRODUCTION: Stem cells from human exfoliated deciduous teeth (SHED) have gained increasing attention in regenerative medicine. However, direct stem cell transplantation faces limitations such as cell survival, manufacturing consistency, genetic instability during expansion, immune compatibility, and potential tumorigenic risk. This review examines advances in SHED-based cell therapies as a biological and therapeutic foundation for emerging cell-free strategies, with emphasis on their mechanisms, regenerative applications, and translational challenges. DATA: A comprehensive literature search was conducted to identify studies focusing on SHED-based regeneration, SHED-derived cell-free components, including secretomes, extracellular vesicles (EVs), extracellular matrix (ECM), conditioned medium (CM), and decellularized matrices. SOURCES: The data sources included PubMed and Web of Science, encompassing peer-reviewed articles published in recent years regarding SHED and regenerative medicine. STUDY SELECTION: Studies were selected based on their relevance to SHED biological characteristics, cell-based therapeutic applications, and limitations of viable-cell transplantation, together with the mechanisms and regenerative applications of SHED-derived cell-free strategies. Preference was given to preclinical studies demonstrating the regenerative potential and clinical applicability of these alternatives to live cell therapies. CONCLUSIONS: Studies of SHED-based cell therapies support their regenerative potential and provide a biological foundation for developing cell-free strategies. Preclinical evidence indicates that SHED-derived products can support tissue repair through bioactive molecules and modulation of the host microenvironment. These emerging approaches may address some limitations of viable-cell transplantation, but standardized preparation, mechanistic validation, and further evaluation of safety and clinical efficacy are required for translation. CLINICAL SIGNIFICANCE: The transition to SHED-derived cell-free therapies marks a pivotal advancement in regenerative medicine. By harnessing selected functional activities of viable cells while avoiding associated risks, these therapies offer a "ready-to-use" therapeutic modality for tissue regeneration. With reproducible manufacturing, appropriate delivery strategies, and demonstrated safety and efficacy, they may enhance the precision and feasibility of regenerative dentistry and broader tissue repair.

doi.org/10.1016/j.jdent.2026.107141 PubMed 42951002 Interventions