Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate the Pancreatic Changes of Chemically Induced Hypothyroidism by Carbimazole in Male Rats

Abstract

We induced hypothyroidism (HT) in male rats through chronic oral administration of carbimazole and then tested whether an i.v. injection of rat bone marrow-derived mesenchymal stem cells (BM-MSCs) could ameliorate the HT-induced changes in pancreatic structure and function. The thyroid and pancreatic function tests, as well as total antioxidant capacity (TAC) and malondialdehyde (MDA) were estimated. The pancreatic structure was evaluated by hematoxylin and eosin (H&E) stain. Insulin protein and cleaved caspase-3 were detected immunohistochemically. The degree of apoptosis was assessed by TUNEL assay. The morphometric measurements were done by an image analyzer system and the obtained data were statistically analyzed. HT rats showed hyperglycemia associated with insulin deficiency, decreased TAC and increased MDA levels. H&E-stained sections showed that the pancreatic septa were infiltrated with acidophilic material. Some acini were vacuolated while others showed depleted acidophilia and dilated lumina. Spindle-shaped cells were accumulated within deformed islets in HT rats. The positive reaction with anti-cleaved caspase-3 was exclusively noted in the cytoplasm of islet cells with no immunostaining reaction in the acinar and ductal cells, whereas the positively stained nuclei with TUNEL were demonstrated in the islet and acinar cells. A significant increase in the apoptotic index % of both markers was detected. Injection of BM-MSCs in HT rats restored all biochemical indicators of disturbed pancreatic function to normal level and improved pancreatic structure, resulting in a clear septa and normal appearance of acini and islets. In conclusion, many of the significant structural and func tional pancreatic alterations detected in HT rats were ameliorated after the injection of BM-MSCs. These data demonstrate the ability of BM-MSCs to repair pancreatic disturbances. Further studies on humans are necessary to determine the potential clinical applications of BM-MSCs.

Effect of Bone Marrow Derived-Mesenchymal Stem Cells on Submandibular Salivary Glands of Carbimazole Induced Hypothyroidism in Albino Rats

“…Moreover, extensive vacuolation was clearly evident within the acinar and ductal cytoplasm of group II. This comes in agreement with previous study which reported shrinkage in the acini and cytoplasmic vacuolation in pancreatic tissue of hypothyroid rats (16) .…”

Effect of Induced Hyperthyroidism on Pancreas of Adult Female Albino Rats

“…H and E-stained slices of the pancreas of control rats revealed the following findings in the current study: normal architecture this was in agreement with Arafa et al (21) who described that it was formed of serous acini in which the cells were pyramidal in shape with round nuclei at the base of the cell. The cytoplasm appeared basal basophilic and apical acidophilic.…”

The Potential Therapeutic Effect of Allogenic Bone Marrow Derived Mesenchymal Stem Cells on Carbimazole-Induced Hypothyroidism on Albino Rats’ Tongue.

“…It was mentioned that thyroid hormones have a well-known effect in the maturation of fungiform papilla. Thus, hypothyroidism could act as a damaging factor for the development of the papillae with subsequent decrease in taste perception (25) .…”

“…The improvement in BM-MSC treated group might be explained by several potential mechanisms. First; indirectly as systemic injection of BM-MSCs may cause regeneration of the thyroid gland (25) . Secondly; directly by homing of injected BM-MSCs in the tongue papillae and trans-differentiation into a diversity of cell types needed for tissue regeneration (14) , this explanation was supported here by the fluorescent PKH26 labeled cells detection within the tissues of the tongue.…”