Dental Pulp Stem Cells Ameliorate Elastase-Induced Pulmonary Emphysema by Regulating Inflammation and Oxidative Stress

Abstract

Background

Dental pulp stem cells (DPSCs) are considered excellent candidates for stem cell-based tissue regeneration. In this study, we aimed to evaluate the therapeutic effect of DPSCs in a mouse chronic obstructive pulmonary disease (COPD) model and to explore whether DPSCs reduce lung inflammation and oxidative stress by regulating the nuclear factor erythroid‐2 related factor‐2 (Nrf2) signaling pathway.

Methods

DPSCs were isolated from dental pulp tissue by the tissue block method. Emphysema of C57BL/6 mice was induced by endotracheal administration of porcine pancreatic elastase (PPE). Then, the DPSCs were injected into the lungs through the trachea, and after 3 weeks of stem cell treatment, various efficacy tests were performed. The AniRes2005 animal lung function analytic system was used to detect lung function. Hematoxylin-eosin staining (H&E) and Victoria blue staining was used to assess emphysema severity. The animal tissues were detected by Western blot, RT‒qPCR, ELISA and oxidative stress related detection.

Results

In experimental COPD models, DPSCs transplantation improved lung function, body weight, and emphysema-like changes better than bone marrow mesenchyml stem cells (BM-MSCs). Compared with the COPD group, the levels of IL-1β, TNF-α and IL-6 in lung tissue and bronchoalveolar lavage fluid (BALF) were decreased after transplantation of DPSCs. DPSCs may be associated with lower malondialdehyde (MDA) levels, and higher catalase (CAT) and glutathione (GSH) levels. Western blot results showed that the expression of Nrf2 and its downstream factors increased after transplantation of DPSCs.

Conclusion

The current study showed that DPSCs had good performance in the treatment of a mouse COPD model and could be a promising option for stem cell therapy. DPSCs may play antioxidant and anti-inflammatory roles in COPD by activating the Nrf2 signaling pathway.

Keywords:

• chronic obstructive pulmonary disease
• dental pulp stem cells
• Nrf2
• inflammation
• oxidative stress

Abbreviations

DPSCs, dental pulp stem cells; COPD, chronic obstructive pulmonary disease; Nrf2, nuclear factor erythroid‐2 related factor‐2; PPE, porcine pancreatic elastase; H&E, hematoxylin-eosin staining; BALF, bronchoalveolar lavage fluid; MDA, malondialdehyde; CAT, catalase; GSH, glutathione; ROS, reactive oxygen species; MSCs, mesenchymal stromal cells; BM-MSCs, bone marrow mesenchymal stem cells; FBS, foetal bovine serum; α-MEM, alpha Modified Eagle Medium; FEV0.1/FVC, the ratio of forced expiratory volume in 0.1 s to forced vital capacity; RL, resistance of lung; Cydn, respireatory dynamic compliance; MLI, mean linear intercept.

Ethics Approval and Consent to Participate

All animal procedures were approved by the ethical standards of the Animal Ethics Committee of Capital Medical University and were conducted in accordance with the “Guide for the Care and Use of Laboratory Animals published by the US NIH (NIH publication No. 85-23, revised 2011)” and Basel Declaration. All human procedures were approved by the institutional ethical Committee of Beijing Chaoyang Hospital Affiliated with Capital Medical University. All study donors provided written informed consent, in accordance with the Declaration of Helsinki.

Author Contributions

Zuomin Wang conceived and designed the study, and reviewed the article critically. Xiaoli Gao performed the experiment and wrote the manuscript. Zhiqiang Liu analyzed and interpreted the data, and substantially revised the article. All authors give final approval to the journal to which the article will be submitted and agreed to all versions of the article. All authors agree to take responsibility for the content of the article.

Disclosure

The authors declare that they have no conflicts of interest.