DPSCs Protect Architectural Integrity and Alleviate Intervertebral Disc Degeneration by Regulating Nucleus Pulposus Immune Status

Dong, Xiwen; Hu, Fanqi; Yi, Jing; Zhang, Yuning; Liu, Chao; Geng, Panpan; Duan, Han; Wu, Chu-Tse; Zhang, Xuesong; Wang, Hua

doi:10.1155/2022/7590337

Cited by 7 publications

(11 citation statements)

References 41 publications

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“…Mesenchymal stem cells have emerged as a promising therapeutic avenue for inflammatory and fibrotic diseases. Among them, DPSCs have also demonstrated their potential to treat various conditions [ 52 , 53 ]. Herein, we investigated the use of DPSCs to treat OSF, a condition characterized by changes in the tissue immune microenvironment, through a novel target.…”

Section: Discussionmentioning

confidence: 99%

DPSCs regulate epithelial-T cell interactions in oral submucous fibrosis

Wang,

Zhang,

Meng

et al. 2024

Stem Cell Res Ther

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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.

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Section: Discussionmentioning

confidence: 99%

DPSCs regulate epithelial-T cell interactions in oral submucous fibrosis

Wang,

Zhang,

Meng

et al. 2024

Stem Cell Res Ther

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“…MSCs have emerged as a promising therapeutic avenue for in ammatory and brotic diseases. Among them DPSCs have also demonstrated potential in treating various conditions (53)(54)(55). Herein, we investigated the use of DPSCs to treat OSF ,We investigated the use of DPSCs to treat OSF through a novel target a condition characterized by changes in the tissue immune microenvironment.…”

Section: Discussionmentioning

confidence: 99%

DPSCs Regulate Epithelial-T Cells Interactions in Oral Submucous Fibrosis

Wang,

Zhang,

Meng

et al. 2023

Preprint

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Background Oral submucous fibrosis (OSF) is a precancerous lesion characterized by fibrous tissue deposition, and the incidence is positively correlated with the degree of betel nut chewing. Prolonged betel nut chewing can damage the integrity of oral mucosal epithelium, leading to chronic inflammation and local immunological derangement, while the underlying cellular events driving fibrogenesis and dysfunction are incompletely understood. Currently, 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. Methods A human cell atlas of oral mucosal tissues using single-cell RNA sequencing to delve into the underlying mechanisms was compiled. The epithelial cells were re-clustered to observe the heterogeneity of OSF epithelial cells and the cell communication relationship 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, SEM and AFM. Results A unique epithelial cell population, Epi1.2, with proinflammatory and profibrotic functions was predominantly found in OSF. They also induced the fibrosis process in fibroblasts by interacting with T cells through the 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 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 were mediated immune homeostasis primarily by regulating the numbers of Epi1.2 and epithelial-stromal crosstalk. Conclusions Given the current ambiguity surrounding the cause of OSF and the limited treatment options available, our work provides new insights into the mechanism of OSF and reveals the therapeutic promise of DPSCs.

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“…DPSC, a type of MSCs derived from dental pulp, have been shown to have therapeutic effects in many diseases [ 32 – 35 ]. However, there is much controversy about the role of MSCs in cancer.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effects of the nanoscale lysate derived from xenogenic dental pulp stem cells in lung cancer models

He,

Li,

She

et al. 2023

J Nanobiotechnol

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Background Lung cancer is a highly prevalent malignancy and has the highest mortality rate among all tumors due to lymph node metastasis. Bone marrow and umbilical cord-derived mesenchymal stem cells (MSCs) have demonstrated tumor-suppressive effects on lung cancer. This study investigated the effects of DPSC lysate on proliferation, apoptosis, migration and invasion of cancer cells were studied in vivo and in vitro. Methods The proliferation, apoptosis, and migration/metastasis were evaluated by cell counting kit-8 assay, Annexin-V and propidium iodide staining, and the transwell assay, respectively. The expression levels of apoptosis-, cell cycle-, migration-, and adhesion-related mRNA and proteins were measured by qRT-PCR and western blot. The level and mRNA expression of tumor markers carcino embryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma (SCC) were measured by Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR. Finally, a tumor-bearing mouse model was constructed to observe the tumor-suppressive effect of DPSC lysate after intraperitoneal injection. Results DPSC lysate decreased the viability of A549 cells and induced apoptosis in lung cancer cells. Western blot confirmed that levels of Caspase-3, Bax, and Bad were increased, and Bcl-2 protein levels were decreased in A549 cells treated with DPSC lysate. In addition, DPSC lysate inhibited the migration and invasion of A549 cells; downregulated key genes of the cell cycle, migration, and adhesion; and significantly suppressed tumor markers. Xenograft results showed that DPSC lysate inhibited tumor growth and reduced tumor weight. Conclusions DPSC lysate inhibited proliferation, invasion, and metastasis; promoted apoptosis in lung cancer cells; and suppressed tumor growth- potentially providing a cell-based alternative therapy for lung cancer treatment. Graphical Abstract

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DPSCs Protect Architectural Integrity and Alleviate Intervertebral Disc Degeneration by Regulating Nucleus Pulposus Immune Status

Cited by 7 publications

References 41 publications

DPSCs regulate epithelial-T cell interactions in oral submucous fibrosis

DPSCs regulate epithelial-T cell interactions in oral submucous fibrosis

DPSCs Regulate Epithelial-T Cells Interactions in Oral Submucous Fibrosis

Inhibitory effects of the nanoscale lysate derived from xenogenic dental pulp stem cells in lung cancer models

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