DPSCs regulate epithelial-T cell interactions in oral submucous fibrosis

Wang，S. Y.1; Zhang，S. J.2; Meng，H. F.3; Xu，H. Q.1,4; Guo，Z. X.1; Yan，J. F.1; Gao，J. L.2; Niu，L. N.2; Wang，S. L.5,6; Jiao，K.1

2024-12-01

10.1186/s13287-024-03720-5

Stem Cell Research and Therapy   影响因子和分区

1757-6512

Background: Oral submucous fibrosis (OSF) is a precancerous lesion characterized by fibrous tissue deposition, the incidence of which correlates positively with the frequency of betel nut chewing. Prolonged betel nut chewing can damage the integrity of the oral mucosal epithelium, leading to chronic inflammation and local immunological derangement. However, currently, the underlying cellular events driving fibrogenesis and dysfunction are incompletely understood, such that OSF has few treatment options with limited therapeutic effectiveness. Dental pulp stem cells (DPSCs) have been recognized for their anti-inflammatory and anti-fibrosis capabilities, making them promising candidates to treat a range of immune, inflammatory, and fibrotic diseases. However, the application of DPSCs in OSF is inconclusive. Therefore, this study aimed to explore the pathogenic mechanism of OSF and, based on this, to explore new treatment options. Methods: A human cell atlas of oral mucosal tissues was compiled using single-cell RNA sequencing to delve into the underlying mechanisms. Epithelial cells were reclustered to observe the heterogeneity of OSF epithelial cells and their communication with immune cells. The results were validated in vitro, in clinicopathological sections, and in animal models. In vivo, the therapeutic effect and mechanism of DPSCs were characterized by histological staining, immunohistochemical staining, scanning electron microscopy, and atomic force microscopy. Results: A unique epithelial cell population, Epi1.2, with proinflammatory and profibrotic functions, was predominantly found in OSF. Epi1.2 cells also induced the fibrotic process in fibroblasts by interacting with T cells through receptor-ligand crosstalk between macrophage migration inhibitory factor (MIF)-CD74 and C-X-C motif chemokine receptor 4 (CXCR4). Furthermore, we developed OSF animal models and simulated the clinical local injection process in the rat buccal mucosa using DPSCs to assess their therapeutic impact and mechanism. In the OSF rat model, DPSCs demonstrated superior therapeutic effects compared with the positive control (glucocorticoids), including reducing collagen deposition and promoting blood vessel regeneration. DPSCs mediated immune homeostasis primarily by regulating the numbers of KRT19 MIF epithelial cells and via epithelial-stromal crosstalk. Conclusions: Given the current ambiguity surrounding the cause of OSF and the limited treatment options available, our study reveals that epithelial cells and their crosstalk with T cells play an important role in the mechanism of OSF and suggests the therapeutic promise of DPSCs.

Cellular microenvironment Dental pulp Epithelial cells Fibrosis Inflammation Single-cell gene expression analysis Stem cells

SCI

英语

其他

2-s2.0-85191079299

Scopus

1.Department of Stomatology,Tangdu Hospital & amp; State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration & amp; School of Stomatology,The Fourth Military Medical University,Xi’an,169 West Changle Road, Xincheng District, Shaanxi,710032,China
2.State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration & amp; National Clinical Research Center for Oral Diseases & amp; Shaanxi Key Laboratory of Stomatology,School of Stomatology,The Fourth Military Medical University,Xi’an,169 West Changle Road, Xincheng District, Shaanxi,710032,China
3.Beijing SH Bio-tech Co.,Beijing,100071,China
4.The College of Life Science,Northwest University,Xi’an,Shaanxi,710032,China
5.Beijing Laboratory of Oral Health,Capital Medical University,Beijing,10 Xitoutiao, Fengtai District,100069,China
6.Laboratory of Homeostatic Medicine,School of Medicine,Southern University of Science and Technology,Shenzhen,No. 1088 Xueyuan Avenue, Nanshan District,518055,China

Wang，S. Y.,Zhang，S. J.,Meng，H. F.,et al. DPSCs regulate epithelial-T cell interactions in oral submucous fibrosis[J]. Stem Cell Research and Therapy,2024,15(1).

Wang，S. Y..,Zhang，S. J..,Meng，H. F..,Xu，H. Q..,Guo，Z. X..,...&Jiao，K..(2024).DPSCs regulate epithelial-T cell interactions in oral submucous fibrosis.Stem Cell Research and Therapy,15(1).

Wang，S. Y.,et al."DPSCs regulate epithelial-T cell interactions in oral submucous fibrosis".Stem Cell Research and Therapy 15.1(2024).