Stem cells from human exfoliated deciduous teeth (SHED) possess bone regeneration ability and may have therapeutic applications. CD146, a cell adhesion protein expressed by vascular endothelial cells, is involved in the osteoblastic differentiation of stem cells. However, the effect of CD146 on SHED-mediated bone regeneration in vivo remains unknown. Hence, in this study we aimed to establish efficient conditions for SHED transplantation. SHED were isolated from the pulp of an extracted deciduous tooth and cultured, and CD146-positive (CD146+) and CD146-negative (CD146−) populations were sorted. Heterogeneous populations of SHED and CD146+ and CD146– cells were transplanted into bone defects generated in the skulls of individual immunodeficient mice. Micro-computed tomography was performed immediately post-transplantation and at 4- and 8-weeks thereafter to evaluate bone regeneration. Histological and immunohistochemical assessments were also performed at 8 weeks after transplantation. Micro-computed tomography revealed bone regeneration upon transplantation with CD146+ and heterogeneous populations of SHED, particularly at 8 weeks after transplantation, with significantly higher bone regeneration observed following transplantation with CD146+ cells. Furthermore, histological and immunohistochemical assessments revealed that CD146+ cells promoted bone regeneration and angiogenesis. Therefore, transplantation of CD146+ SHED into bone defects may serve as a useful strategy for bone regeneration.