The thyroid gland is an essential endocrine gland that secretes thyroid hormones (Al-Suhaimi & Khan, 2022). These hormones control the heartbeat, body temperature, bone marrow development, reproduction, development of bone, and the gastrointestinal motility (Al-Suhaimi and Khan, 2022, Baksi and Pradhan, 2021). They are also pivotal for lipid, carbohydrate, protein metabolism, oxygen consumption and energy metabolism. In addition, they play a role in keratinocyte proliferation, wound healing and regulating the keratin genes (Barreiro Arcos, 2022, Mancino et al., 2021, Teixeira et al., 2020). Thyroid gland dysfunction can lead to hypothyroidism which is characterized by thyroid hormone deficiency. Hypothyroidism can also occur as a complication while taking antithyroid drug including carbimazole (Farag et al., 2023, Sfeir and Gharib, 2022). Hypothyroidism is associated with loss of appetite, lower motility of the gastrointestinal tract, alteration in the salivary gland histology and enlarged tongue (Chaker et al., 2022, Mohammed et al., 2022, Zamwar and Muneshwar, 2023).

The tongue is a mobile organ consisting mainly of muscles and is vital for swallowing, taste, and speaking. It consists of two parts; the oral and the pharyngeal parts. The dorsal lingual mucosa of the oral part contains papillae which consist of keratinized surface epithelium and underlying connective tissue. The inferior surface of the tongue is covered by lining mucosa consisting of non-keratinized stratified epithelium and an underlying thin layer of lamina propria (Nanci, 2018).

The mesenchymal stem cells (MSCs) are unique cells, in being easy to isolate, grow, and can home to injured areas. They also have antibacterial, anti-inflammatory, and anti-apoptotic properties as well as a paracrine immunomodulatory activity. They have the ability to increase neo-angiogenesis and endogenous stem cells (Maacha et al., 2020, Yang et al., 2023). One of the earliest known MSCs and the most developed in clinical trials is bone marrow derived MSCs (BM-MSCs). They can be specified into distinct lineages of endodermal and ectodermal cells in addition to the mesodermal lineage that includes bone, cartilage, and adipocytes (Bhartiya et al., 2023, Kozlowska et al., 2019).

Previous studies reported that the BM-MSCs have an ameliorative effect on the pathological changes in different organs including the pancreas (Arafa et al., 2019), submandibular salivary glands (Ahmed et al., 2023), and in bone healing (Sefati et al., 2018). Furthermore, BM-MSCs and derivatives improved the structural changes in the tongue of diabetic rats (Halawa et al., 2023, Mohsen et al., 2019, Radwan et al., 2024), tongue of irradiated rats (Elsaadany et al., 2017), circumvallate papillae of ovariectomized rats with induced Alzheimer disease (Hassan et al., 2020) and the tongue of hypothyroid rats (Reyad & Abdel Moneim, 2021; Reyad, Adawy et al., 2021).

Systemic infusion of BM-MSCs have a regenerative effect on the lingual changes of hypothyroid rats (Reyad & Abdel Moneim, 2021; Reyad, Adawy et al., 2021), however, there is a lack in explaining the scientific basis of this regenerative effect. In addition, the role of the local infusion of BM-MSC in the tongue of hypothyroid rats was not assessed. Therefore, this study was conducted to test the efficiency of locally injected BM-MSCs in improving the prospective histopathological alterations in the hypothyroid rat tongue and to uncover the potential mechanism by which BM-MSCs ameliorate these changes. Our null hypothesis was that the locally infused BM-MSCs do not affect the prospective structural changes in the lingual epithelium of the hypothyroid rats.