Dental pulp stem cells promote malignant transformation of oral epithelial cells through mitochondrial transfer.

IF 1.2 4区医学 Q3 PATHOLOGY

Medical Molecular Morphology Pub Date : 2024-12-01 Epub Date: 2024-08-09 DOI:10.1007/s00795-024-00403-1

Peiqi Shen, Zeyi Ma, Xiaoqing Xu, Weiyu Li, Yaoyin Li

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Abstract

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.

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牙髓干细胞通过线粒体转移促进口腔上皮细胞恶性转化

口腔上皮发育不良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（DPSC）是针对各种疾病的细胞疗法的潜在候选者。然而，牙髓干细胞对口腔黏膜癌前病变进展的影响仍不清楚。为了评估人DPSCs（hDPSCs）的影响，我们进行了动物实验。我们测量了与 hDPSCs 共同培养的人类发育不良口腔角质细胞（DOK）的增殖、运动和线粒体呼吸功能。hDPSCs注射可加速4NQO诱导的小鼠口腔上皮发育不良的癌变。与 hDPSCs 共培养可增加 DOK 细胞的增殖、迁移、侵袭和线粒体呼吸功能。hDPSCs的线粒体可转移到DOK细胞，并激活DOK细胞的mTOR信号通路。我们的研究表明，hDPSCs通过线粒体转移激活了mTOR信号通路，促进了口腔癌前上皮病变的恶性转化。

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来源期刊

Medical Molecular Morphology 医学-病理学

CiteScore

2.90

自引率

5.60%

发文量

审稿时长

>12 weeks

期刊介绍： Medical Molecular Morphology is an international forum for researchers in both basic and clinical medicine to present and discuss new research on the structural mechanisms and the processes of health and disease at the molecular level. The structures of molecules, organelles, cells, tissues, and organs determine their normal function. Disease is thus best understood in terms of structural changes in these different levels of biological organization, especially in molecules and molecular interactions as well as the cellular localization of chemical components. Medical Molecular Morphology welcomes articles on basic or clinical research in the fields of cell biology, molecular biology, and medical, veterinary, and dental sciences using techniques for structural research such as electron microscopy, confocal laser scanning microscopy, enzyme histochemistry, immunohistochemistry, radioautography, X-ray microanalysis, and in situ hybridization. Manuscripts submitted for publication must contain a statement to the effect that all human studies have been reviewed by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in an appropriate version of the 1964 Declaration of Helsinki. It should also be stated clearly in the text that all persons gave their informed consent prior to their inclusion in the study. Details that might disclose the identity of the subjects under study should be omitted.