B7H3 is a member of B7 family of immunoregulatory transmembrane glycoproteins associated with maintaining immune tolerance, tumor cell proliferation, migration, invasion and metabolism, drug resistance, and stem cell differentiation. Neural crest-derived Multipotent Stem Cells (MSCs) from the dental pulp has become a good choice for tissue regeneration because it is easily obtainable and has strong regeneration potentials. Although there have been many studies investigating the role of B7H3 in cancer cells and immune cells, its role in the dental pulp stem cells regeneration is unknown. In this study, we chose SHEDs (stem cells from human exfoliated deciduous teeth) as a research model to analyze the expression and function of B7H3. The result showed that SHEDs were B7H3/CD90, B7H3/ CD73, B7H3/CD105 double positive, and the expression of B7H3 is primarily located within the membrane. Downregulation of B7H3 expression significantly accelerated the expansion of SHEDs through the SHP1/AKT signal axis while upregulation of B7H3 expression decreased the proliferation of SHEDs. Hence, this study indicates that B7H3 is a stem cell surface molecule and might be used as a SHEDs marker whereby its downregulation enhances the proliferation of SHEDs via the activation of B7H3/ SHP1/AKT signaling pathway. (C) 2020 Elsevier Inc. All rights reserved.