Reconstruction of necrotic submandibular salivary gland using mesenchymal stem cells

Abstract

Background The efficacy of mesnchymal stem cells (MSCs) to treat the necrotic tissue of salivary glands (SGs) has yet investigated. Objective This study was conducted to investigate the potential capacity of MSCs to restore the function and regenerate the necrotic submandiular gland in the rat animal model. Methods Twenty-one Sprague–Dawley rats were provided from a breeding colony and randomly divided into three groups including the positive control or induced SG atrophy without treatment, the treatment group or induced SG atrophy with MSCs isolated transplantation and the negative control group consists of healthy rats. The atrophic and necrotic submandiular gland was induced using intraoral duct ligation of the main duct of submandiular gland for one month. The isolated stem cells were confirmed using flow cytometry for CD90 and CD 105. The isolated MSCs were cultured and injected to submandiular gland and the potential efficacy of MSCs to treat the atrophic submandibular glands was evaluated using histopathology on two weeks post-transplantation. To detect the acinar cell protein secretory granules, Alcian Blue and periodic acid shift (PAS) staining were done. For the demonstration of mitotic index or proliferation rate of the SG epithelia tissue, Ki-67 and Smbg proteins expression were evaluated using immunohistochemistry. Results The locally injected MSCs could regenerate the overall histological structure of the necrotic submandibular gland tissue within 2 weeks of post-transplantation. Alcian Blue and PAS staining indicated that the mean amount of serous and mucin secretions in the treatment group was significantly increased compared to the positive control groups. We have also found that the treatment group significantly express higher Ki-67 protein, as a diagnostic marker for cell mitosis and proliferation rate, and lower Smbg protein, as a diagnostic marker, for damage to the submandibular gland than that of control group. Conclusion This study demonstrates the therapeutic benefits of MSCs isolated from the SG in treating atrophic and necrotic SGs in a rat model. MSCs may be potential candidates for cell-based therapies targeting hypofunction of SG induced by a range of diseases or because of surgery and radiotherapy of head and neck cancers.

Efficacy of mesenchymal stem cell therapy in rodent models of radiation-induced xerostomia and oral mucositis: a systematic review

“…[ 60 ]. (3) Secretion of soluble factors [ 61 ], such as mesenchymal stem cells can secrete fibroblast growth factor [ 28 ], and one of its members, keratinocyte growth factor (KGF), can promote the proliferation of oral epithelial cells and enhance the radiation resistance of oral epithelial cells, thus improving radiation oral mucositis [ 62 , 63 ].…”

“…Special attention is paid to the fact that in recent years, MSCs have been widely used in various inflammatory diseases and salivary gland injury diseases. Since MSCs have functions such as directed differentiation [ 24 ], regulation of immunity [ 25 ], antioxidant [ 26 ], anti-apoptosis [ 27 ], promotion of cell regeneration [ 28 ], and angiogenesis [ 29 ], they have good therapeutic effects in various inflammatory diseases and salivary gland injury diseases.…”

Retroductal Delivery of Epidermal Growth Factor Protects Salivary Progenitors after Irradiation

“…Given that radiation-induced salivary gland hypofunction elicits dysphagia, dysarthria, poor oral hygiene, oral candidiasis, and dental caries, the protection of salivary gland progenitors’ reparative potentials during radiotherapy may reduce these xerostomia-related discomforts and diseases after radiotherapy. Many other therapeutics, including stem cells and their derivatives, have been investigated regarding whether they can protect radiotherapy-damaged salivary gland cells (Lim, Ra, et al 2013; Lim, Yi, et al 2013; Lombaert et al 2017; Shin et al 2018; Kim et al 2019; Najafi et al 2020). The therapeutic efficacies of these candidates should be further compared, and administration routes, retroductal delivery versus direct local or systemic administration, remain to be also investigated to determine which therapeutic strategy will benefit patients with salivary gland hypofunction resulting from radiation therapy.…”

The NF-κB pathway plays a vital role in rat salivary gland atrophy model

“…A gradual increase in intraductal pressure is the main cause of salivary gland atrophy with duct ligation, affecting the acinar and ductal epithelial cells [ 14 ]. Cell proliferation markers are upregulated when mesenchymal stem cells are used to treat the necrotic tissue of salivary glands in a rat submandibular gland duct ligation model [ 15 ]. The regeneration process is initiated by duct ligation as part of self-repair, thus activating Wnt/β-catenin signaling, which then promotes regeneration of the salivary gland [ 16 ].…”