الفهرس 
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Abstract
The aim of the present investigation was study the effect of the use of bone marrow derived stem cells in reversing the degenerative effect of STZ-induced diabetes mellitus on the submandibular salivary glands and pancreatic islets of Langerhans in albino rats.Materials and methods:A Total of sixty, adult male albino rats with body weight ranging from 180-200 grams were used in the present investigation. They were devided as follows:- group 1.1: consisted of 15 animals and served as controls.- group 2.1: consisted of 15 animals, they were subjected to a single intraperitoneal injection of streptozotocin in a dose of 60 mg/kg body weight dissolved in 0.1 M. citrate buffer PH 4.5 for induction of diabetes mellitus. - group 3 : consisted of 30 animals, they were subdivided as follows:- Subgroup 3.1: consisted of 15 animals, they were used for isolation and culture of bone marrow stem cells.-Subgroup 3.2: consisted of 15 animals, they were subjected to a single intraperitoneal injection of streptozotocin, the same as group 2.1, in a dose of 60 mg/kg body weight for induction of diabetes mellitus. One week later, they were subjected to a single intravenous infusion of mesenchymal bone marrow stem cells. to study the effect on the submandibular salivary glands and pancreatic islets cells of diabetic rats.At the end of the experiment the animals of the different groups were sacrificed by cervical dislocation, their submandibular salivary glands will be dissected out, separated into right and left glands. Those of the right side were fixed in 10% neutral buffered formalin, processed and embedded in paraffin. Six microns thick sections were cut to be stained with hematoxylin and eosin for histological examination to detect any structural changes in the paranchymal and stromal elements of the glands. Specimens of the left side were used for transmission electron microscopic examination. Small pieces of average size 1 cubic mm were immediately cut, rapidly fixed in 3% phosphate buffered gluteraldehyde, post fixed in 1% buffered osmium tetroxide, then embedded in epoxy resin. Ultrathin sections were cut to be stained with uranyl acetate and lead citrate to be examined using TEM (Joel 1000) in the Cancer Institute Cairo University. The pancreas of rats of all groups were dissected out at the proposed time of their sacrifice, fixed, processed, embedded in paraffin to be sectioned and stained with hematoxylin and eosin to study the condition of the islets of Langerhans.Results:I. Histological Results using Hematoxylin and eosin stained sections:. group 1.1 animals ( control group)the histological examination of the control group revealed the normal histology of the submandibular salivary glands, being composed of acinar portions and duct system within normal C.T. stroma.The pancreas was formed of normal C.T stroma and parenchyma with large islets of Langerhans showing normal cells .2. group 2.1 animals (diabetic group)The most outstanding and common finding was the apparent reduction in the size and number of the secretory terminal portions and ducts of the submandibular salivary gland with marked spacing between acini.The acinar cells showed numerous intracytoplasmic vacuolizations and reduced basophilia of their cytoplasm. The GCTs revealed decreased eosinophilic granular content and areas of degeneration could be seen in their lining cells. The striated duct cells revealed numerous intracytoplasmic vacuolizations and shrinkage of their nuclei and excretory ducts revealed thinning of their epithelial lining with stagnated secretion in their wide lumen.The C.T stroma revealed increased fibrous content with dilated blood vessels engorged with RBCs and inflammatory cells infiltration.The pancreas of the diabetic rats showed degeneration of the islets of Langerhans ranging from cytoplasmic vacuolization to total disappearance of cells with marked shrinkage of the size of the islets. There was marked dilatation of blood vessels in the surrounding reticular connective tissue.3. Subgroup 3.2 animals (diabetic injected with MBMDSCs):There was marked improvement in the structural elements of the submandibular salivary gland. There was total or subtotal absence of the intracytoplasmic vacuolizations both in the secretory terminal portions and ducts of the diabetic rats.The GCT regained their eosinophilic and granular content of their cytoplasm and the ducts regained their normal lining and lumena with no retained secretion.The connective tissue stroma appeared normal with absence of inflammatory cells and normally appearing blood vessels.The pancreas of the diabetic rats that were treated with a single intravenous infusion of mesenchymal bone marrow derived stem cells showed regeneration of the cells of the islets of Langerhans that regained their normal size. Dilated blood vessels in the surrounding reticular connective tissue were sometimes encountered.II. Ultrastructural results using Transmission electron microscope (TEM):1. group 1.1 animals ( control group)The submandibular salivary gland of the control group revealed normal ultrastructural findings with normal acinar and duct cells appearance, normal cell organelles and desmosomal junctions and junctional complexes were frequently seen between cells. The connective tissue stroma were formed of moderately dense collagen fibers, fibroblasts, rich with their different types of organelles mainly RER, mitochondria and Golgi apparatus together with an oval euchromatic nuclei.Blood vessels lined by endothelial cells and filled with electron dense red blood corpuscles were seen2. group 2.1 animals (diabetic group)Electron microscopic examination of the submandibular salivary glands of diabetic rats revealed marked degenerative changes in the ultrastructure of its parenchymal and stromal elements.
Their were marked intractoplasmic vacuolization in the acinar, duct and GCTs cells with pyknotic nuclei with irregular nuclear membranes and mostly heterochromatin. The cells revealed degenerated cell organelles. Marked decrease in the granular content of GCTs, and loss of basal infolding of striated duct cells were consistent findings.
The connective tissue stroma of the gland showed signs of degeneration and dissociation of the collagen fibers, fibroblasts and markedly dilated blood vessels engorged with blood
3. Subgroup 3.2 animals (diabetic injected with MBMDSCs):
They revealed marked regeneration of the parenchymal and C.T elements of the glands with more or less normal findings resembling those of the control group with absence of the degenerative effects changes that were seen in the diabetic group.