Abstract:
Background Mesenchymal stem cells (MSCs) therapy for allergic rhinitis (AR) is a research hotspot in this field, and the effectiveness and mechanism of hepatocyte growth factor (HGF)-overexpressing MSCs in AR treatment remains to be further explored.
Objective To evaluate the function of HGF-overexpressing human dental pulp stem cells (HGF/hDPSCs) in AR treatment and discover the underlying mechanisms in a mouse model.
Methods Firstly, dental pulp stem cells were isolated from human and transfected with the target gene HGF using the Adenovirus 5 (Ad5) vector to create HGF/hDPSCs. The in vivo study was performed to determine the secretion and distribution of HGF in nasal mucosa. An allergic rhinitis mouse model was established through intraperitoneal injection of ovalbumin (OVA) for sensitization and nasal drop for challenge. Based on differences in sensitization, challenge, and intervention, the mice were divided into 4 groups: WT-PBS group (negative control group), AR-PBS group (positive control group), AR-hDPSCs group (hDPSCs treatment group), and AR-HGF/hDPSCs group (HGF/hDPSCs treatment group). Symptom scoring and pathological analysis, including HE and PAS staining, were used to monitor the symptoms of allergic rhinitis and inflammation of the nasal mucosa. Finally, the immune response mechanism was explored using immunohistochemical staining for CD3 and CD19, ELISA for total IgE, and OVA-specific IgE, and qPCR for IFN-γ, IL-5, IL-13, IL-17A, and Foxp3.
Results HGF/hDPSCs expressed HGF stably in vitro and in vivo and migrated to the nasal mucosa after tail vein injection. Symptom scores indicated that HGF/hDPSCs significantly improved allergic symptoms such as nasal scratching, sneezing, and runny nose in mice with allergic rhinitis (P<0.05). Pathological analysis and immunohistochemistry revealed that the nasal mucosal immune response of allergic rhinitis mice was mainly characterized by T lymphocyte aggregation. The application of HGF/hDPSCs significantly reduced nasal mucosal inflammation, including lymphocyte infiltration and goblet cell hyperplasia, as well as pathological damage scores (P<0.01). ELISA results indicated that HGF/hDPSCs could significantly down-regulate the sera levels of total IgE and OVA-specific IgE (P<0.01). The qPCR results indicated that HGF/hDPSCs could inhibit the response of Th1 cells (IFN-γ) and Th2 cells (IL-5, IL-13) in the spleen of mice with allergic rhinitis, thereby altering Th2/Th1 balance. Additionally, HGF/hDPSCs were found to down-regulate the response of Th17 cells (IL-17A) (P<0.05), without any effect on the response of Treg cells (Foxp3) (P>0.05), thus changing the Th17/Treg balance.
Conclusion HGF/hDPSCs have the potential to alleviate nasal allergic symptoms and reduce nasal mucosal inflammation in mice with OVA-induced allergic rhinitis by regulating the Th2/Th1 and Th17/Treg balance.