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, minim...

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Autores principales:	Rasha H. Al-Serwi, Ahmed Othman Fathy Othman El-Kersh, Gehan El-Akabawy
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Dental pulp stem cells Diabetes Streptozotocin Parotid gland Medicine (General) R5-920 Biochemistry QD415-436
Acceso en línea:	https://doaj.org/article/3b42d0177fa54e4195a3f85b96e3b604
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spelling	oai:doaj.org-article:3b42d0177fa54e4195a3f85b96e3b6042021-11-21T12:04:47ZHuman dental pulp stem cells attenuate streptozotocin-induced parotid gland injury in rats10.1186/s13287-021-02646-61757-6512https://doaj.org/article/3b42d0177fa54e4195a3f85b96e3b6042021-11-01T00:00:00Zhttps://doi.org/10.1186/s13287-021-02646-6https://doaj.org/toc/1757-6512Abstract 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.Rasha H. Al-SerwiAhmed Othman Fathy Othman El-KershGehan El-AkabawyBMCarticleDental pulp stem cellsDiabetesStreptozotocinParotid glandMedicine (General)R5-920BiochemistryQD415-436ENStem Cell Research & Therapy, Vol 12, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Dental pulp stem cells Diabetes Streptozotocin Parotid gland Medicine (General) R5-920 Biochemistry QD415-436
spellingShingle	Dental pulp stem cells Diabetes Streptozotocin Parotid gland Medicine (General) R5-920 Biochemistry QD415-436 Rasha H. Al-Serwi Ahmed Othman Fathy Othman El-Kersh Gehan El-Akabawy Human dental pulp stem cells attenuate streptozotocin-induced parotid gland injury in rats
description	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.
format	article
author	Rasha H. Al-Serwi Ahmed Othman Fathy Othman El-Kersh Gehan El-Akabawy
author_facet	Rasha H. Al-Serwi Ahmed Othman Fathy Othman El-Kersh Gehan El-Akabawy
author_sort	Rasha H. Al-Serwi
title	Human dental pulp stem cells attenuate streptozotocin-induced parotid gland injury in rats
title_short	Human dental pulp stem cells attenuate streptozotocin-induced parotid gland injury in rats
title_full	Human dental pulp stem cells attenuate streptozotocin-induced parotid gland injury in rats
title_fullStr	Human dental pulp stem cells attenuate streptozotocin-induced parotid gland injury in rats
title_full_unstemmed	Human dental pulp stem cells attenuate streptozotocin-induced parotid gland injury in rats
title_sort	human dental pulp stem cells attenuate streptozotocin-induced parotid gland injury in rats
publisher	BMC
publishDate	2021
url	https://doaj.org/article/3b42d0177fa54e4195a3f85b96e3b604
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Human dental pulp stem cells attenuate streptozotocin-induced parotid gland injury in rats

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