Dental pulp is critical to maintain the vitality of a tooth. Regeneration of pulpo-dentinal complex is of great interest to treat pulpitis and pulp necrosis. In this study, through three-dimensional spheroid culture, a group of unique multipotent stem cells were identified from mouse dental papilla called multipotent dental pulp regenerative stem cells (MDPSCs). MDPSCs exhibited enhanced osteogenic/odontogenic differentiation capabilities and could form regenerative dentin and neurovascular-like structures that mimicked the native teeth in vivo. Further analysis revealed that CD24a was the bona fide marker for MDPSCs, and their expansion was highly dependent on the expression of a key transcriptional factor, Sp7. Last, CD24a⁺ cells could be detected in primary dental papilla in mice and human, suggesting that MDPSCs resided in their native niches. Together, our study has identified a previously unidentified group of multipotent pulp regenerative stem cells with defined molecular markers for the potential treatment of pulpitis and pulp necrosis.

牙髓对于维持牙齿的活力至关重要。牙髓-牙本质复合体的再生对于治疗牙髓炎和牙髓坏死非常重要。在这项研究中，通过三维球体培养，从小鼠牙乳头中鉴定出一组独特的多能干细胞，称为多能牙髓再生干细胞（MDPSC）。MDPSC表现出增强的成骨/成牙本质分化能力，并可以在体内形成模仿天然牙齿的再生牙本质和神经血管样结构。进一步的分析表明，CD24a是MDPSC的真正标记，它们的扩增高度依赖于关键转录因子Sp7的表达。最后，CD24a ⁺可以在小鼠和人类的原发性牙乳头中检测到细胞，这表明MDPSC位于其天然壁ni中。在一起，我们的研究已经确定了一组以前未鉴定的多能纸浆再生干细胞，这些干细胞具有确定的分子标记物，可用于牙髓炎和牙髓坏死的潜在治疗。