Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou, Guangdong, 510055, People's Republic of China.
Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, Guangdong, China.
Med Mol Morphol. 2024 Dec;57(4):306-319. doi: 10.1007/s00795-024-00403-1. Epub 2024 Aug 9.
Oral epithelial dysplasia includes a range of clinical oral mucosal diseases with potentially malignant traits. Dental pulp stem cells (DPSCs) are potential candidates for cell-based therapies targeting various diseases. However, the effect of DPSCs on the progression of oral mucosal precancerous lesions remains unclear. Animal experiments were conducted to assess the effect of human DPSCs (hDPSCs). We measured the proliferation, motility and mitochondrial respiratory function of the human dysplastic oral keratinocyte (DOK) cells cocultured with hDPSCs. Mitochondrial transfer experiments were performed to determine the role mitochondria from hDPSCs in the malignant transformation of DOK cells. hDPSCs injection accelerated carcinogenesis in 4NQO-induced oral epithelial dysplasia in mice. Coculture with hDPSCs increased the proliferation, migration, invasion and mitochondrial respiratory function of DOK cells. Mitochondria from hDPSCs could be transferred to DOK cells, and activated mTOR signaling pathway in DOK cells. Our study demonstrates that hDPSCs activate the mTOR signaling pathway through mitochondrial transfer, promoting the malignant transformation of oral precancerous epithelial lesions.
口腔上皮异型增生包括一系列具有潜在恶性特征的临床口腔黏膜疾病。牙髓干细胞（DPSCs）是针对各种疾病的基于细胞疗法的潜在候选者。然而，DPSCs 对口腔黏膜癌前病变进展的影响尚不清楚。进行了动物实验以评估人牙髓干细胞（hDPSCs）的作用。我们测量了与人牙髓干细胞共培养的人异型口腔角质形成细胞（DOK）细胞的增殖、迁移和线粒体呼吸功能。进行线粒体转移实验以确定来自 hDPSCs 的线粒体在 DOK 细胞恶性转化中的作用。hDPSCs 注射加速了 4NQO 诱导的小鼠口腔上皮异型增生的癌变。与人牙髓干细胞共培养可增加 DOK 细胞的增殖、迁移、侵袭和线粒体呼吸功能。来自 hDPSCs 的线粒体可以转移到 DOK 细胞中，并激活 DOK 细胞中的 mTOR 信号通路。我们的研究表明，hDPSCs 通过线粒体转移激活 mTOR 信号通路，促进口腔癌前上皮病变的恶性转化。
