Abstract
ObjectiveDiabetes mellitus causes deterioration in the body, including serious damage of the oral cavity related to salivary gland dysfunction, characterised by hyposalivation and xerostomia. Human dental pulp stem cells (hDPSCs) represent a promising therapy source, due to the easy, minimally invasive surgical access to these cells and their high proliferative capacity. It was previously reported that the trophic support mediated by these cells can rescue the functional and structural alterations of damaged salivary glands. However, potential differentiation and paracrine effects of hDPSCs in diabetic-induced parotid gland damage have not been investigated. Our study aimed to investigate the therapeutic effects of intravenous transplantation of hDPSCs on parotid gland injury in a rat model of streptozotocin (STZ)-induced type 1 diabetes.MethodsThirty Sprague–Dawley male rats were randomly categorised into three groups: control, diabetic (STZ), and transplanted (STZ + hDPSCs). The hDPSCs or the vehicles were injected into the rats’ tail veins, 7 days after STZ injection. Fasting blood glucose levels were monitored weekly. A glucose tolerance test was performed, and the parotid gland weight, salivary flow rate, oxidative stress indices, parotid gland histology, and caspase-3, vascular endothelial growth factor, proliferating cell nuclear antigen, neuronal nitric oxide synthase, endothelial nitric oxide synthase, and tetrahydrobiopterin biosynthetic enzyme expression levels in parotid tissues were assessed 28 days post-transplantation.ResultsTransplantation of hDPSCs decreased blood glucose, improved parotid gland weight and salivary flow rate, and reduced oxidative stress. The cells migrated to the STZ-injured parotid gland and differentiated into acinar, ductal, and myoepithelial cells. Moreover, hDPSCs downregulated the expression of caspase-3 and upregulated the expression of vascular endothelial growth factor and proliferating cell nuclear antigen, likely exerting pro-angiogenic and anti-apoptotic effects and promoting endogenous regeneration. In addition, the transplanted cells enhanced the parotid nitric oxide-tetrahydrobiopterin pathway.ConclusionsOur results showed that hDPSCs migrated to and survived within the STZ-injured parotid gland, where functional and morphological damage was prevented due to the restoration of normal glucose levels, differentiation into parotid cell populations, and stimulation of paracrine-mediated regeneration. Thus, hDPSCs may have potential in the treatment of diabetes-induced parotid gland injury.
Highlights
Diabetes mellitus affects almost all organs and organ systems of the body and causes significant damage in the oral cavity [1,2,3,4]
Our results showed that Human dental pulp stem cells (hDPSCs) migrated to and survived within the STZ-injured parotid gland, where functional and morphological damage was prevented due to the restoration of normal glucose levels, differentiation into parotid cell populations, and stimulation of paracrine-mediated regeneration
Characterisation of hDPSCs The hDPSCs from passage 4 were analysed for the expression of CD105, CD29, CD146, CD90, and stromal precursor antigen-1 (STRO-1) and for the expression of CD34, using flow cytometry analysis
Summary
Diabetes mellitus affects almost all organs and organ systems of the body and causes significant damage in the oral cavity [1,2,3,4]. The majority of oral changes related to salivary gland dysfunction are characterised by hyposalivation and xerostomia, which significantly reduce the quality of life in patients with diabetes [5,6,7] Both basal and stimulated secretion of the parotid and submandibular glands are dramatically downregulated under prolonged hyperglycaemia in humans and rats [8,9,10,11]. Diabetes is accompanied by atrophy of the parotid and submandibular salivary glands, as evidenced by reductions in gland weight and size, resulting from degeneration of acinar cells and intralobular ducts [10,11,12,13,14,15,16,17,18] These salivary gland changes are likely caused by diabetesinduced oxidative damage. Upon stimulation, the parotid gland, one of the main salivary glands, secretes more than 50% of the total saliva [21]
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