Human dental pulp stem cells attenuate streptozotocin-induced parotid gland injury in rats

Abstract

Objective Diabetes 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. Methods Thirty 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. Results Transplantation 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. Conclusions Our 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.

Therapeutic potential of dental pulp stem cells and their derivatives: Insights from basic research toward clinical applications

“…The transplantation of DPSCs has been investigated as a potential therapy for a variety of injuries and diseases, including but not limited to stroke[ 64 ], spinal cord injury[ 65 ], cerebellar ataxia[ 66 ], retinal degeneration[ 15 ], diabetic neuropathy[ 67 ], parotid gland injury[ 68 ], cystitis[ 69 ], Sjögren syndrome[ 70 ], etc . In the treatment of these diseases using DPSCs, injection is one of the more commonly used forms.…”

“…In the treatment of these diseases using DPSCs, injection is one of the more commonly used forms. Stem cell injections are the easiest cell therapy products to prepare, and the commonly used vehicles at present for resuspension of stem cells is phosphate-buffered saline[ 69 - 73 ], Hank's Balanced Salt Solution[ 15 ], normal saline[ 14 , 67 , 74 - 76 ], and modified medium[ 66 , 68 , 77 - 79 ]. These mediators have no therapeutic effect and only serve as transport vectors for stem cells, so it is possible to observe the monotherapy effect of transplanted stem cells and rule out the influence of carriers.…”

“…These mediators have no therapeutic effect and only serve as transport vectors for stem cells, so it is possible to observe the monotherapy effect of transplanted stem cells and rule out the influence of carriers. In addition, DPSC injections are usually administered by local injection[ 15 , 66 , 69 , 80 ], intramuscular injection[ 67 , 76 , 81 ] and intravenous injection[ 67 , 68 , 72 , 82 ]. Different methods of administration lead to different systemic distributions and different efficacies.…”

“…Both intravenously and locally injected DPSCs have been shown to improve symptoms of various lesions[ 15 , 72 , 76 , 80 ]. DPSCs have also been shown to migrate and integrate into the site of injuries[ 15 , 69 , 73 , 74 ] and differentiate into corresponding cells[ 68 , 72 , 75 , 79 , 84 ].…”

Ação Combinada Da L-Glutamina E Insulinoterapia Melhora a Morfometria Dos Ácinos Da Parótida De Ratos Diabéticos

“…Através da análise morfométrica, observou-se redução da atrofia acinar na glândula parótida dos ratos diabéticos dos grupos D-S-TRE e D-GLN-TRE em relação aos dos grupos DSS e D-GLN-S; e este dado pode estar relacionado a diversos fatores que influem diretamente na morfofisiologia do parênquima glandular, sobretudo da glândula parótida. Tais fatores são elencados como: modificação na síntese e no conteúdo de proteínas, 17 bem como, redução dos níveis de aquaporinas, que são essenciais para a transferência de água e no equilíbrio eletrolítico na secreção de saliva 18 colaborando com a atrofia; da redução da resposta secretória da parótida às estimulações simpática e parassimpática devido à neuropatia autonômica 19 e a falta de insulina; uma vez que a manutenção da estrutura e função normal do parênquima glandular depende parcialmente deste hormônio. 20 Este último fator, foi observado em nosso estudo, ao constatar que os grupos D-S-TRE e D-GLN-TRE exibiram áreas acinares maiores que os grupos DSS e D-GLN-S.…”