الفهرس 
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Abstract
Diabetes Mellitus is a major medical concern as it is highly prevalent and have potential deleterious effects on patient physical and psychological state. It is a devastating disease which remains incurable and is only controlled with drugs. Replacement of the diseased islet cells, which could be accomplished by using stem cells capable of proliferation and differentiation as well as insulin secretion, would provide a potentially unlimited source of islet cells for transplantation and alleviating the major diabetic complications.
In the current study, rats were randomly divided into four equal groups 10 rats each, as follows: group I (Plain control): received no medications, only standard diet only group II (Sham Control): received a single injection of citrate buffer saline. group III (Diabetic group): received a single injection of streptozotocin group IV (Stem cell group): received a single injection of streptozotocin then after confirmation of diabetes, another single i.v. injection of fluorescent-labeled mesenchymal stem cells was given one week later. Then rats were sacrificed one month following streptozotocin injection. Light microscopy using Hematoxylin and Eosin (Hx. & E.), Gomori stain; selective stain for islet beta cells; in order to detect pathological changes of pancreatic tissue induced by the tested drug and the suspected repair consequent to mesenchymal stem cells and immunofluorescent staining to detect homing of stem cells to pancreatic tissue examined the pancreatic architecture. Fasting blood glucose level was measured in all groups to detect changes in β- cell functional using conventional laboratory methods.
MSCs were derived from the bone marrow of femora and tibiae of adult male Sprague Dawley albino rats. They were separated, grown, propagated in culture for 4 weeks and were characterized by their morphology and multipotentiality of the resulting cells was verified with the use of in vitro assays to differentiate into osteoblasts (Osteogenic differentiation of MSCs). After 14 days, Cells were photographed under an inverted microscope. The MSCs were labeled in vitro for later identification by adding 5-bromo-2ʹ-deoxyuridine containing media to about 70% confluent cultures then resuspended to a concentration of 2×106 bone marrow MSCs in 1mL of culture medium. MSCs were infused into the tail vein of the rats that received streptozotocin injection to induce type 1 DM. Rats were categorized into four groups: plain control, sham control, streptozotocin-treated and MSC-STZ treated .Pancreatic tissue was examined histopathologically and fasting blood sugar were estimated for all groups.
Pancreatic specimens’ examination revealed normal pancreatic architecture in group 1 and 2, pathological changes usually accompanying diabetes in group 3 and reversal of these changes with restoration of normal pancreatic architecture in group 4.Flourescent microscopy examination of stem cell treated group was done to trace the injected stem cells inside the body of the rats. The above mentioned results reflects the potential of mesenchymal stem cells to regenerate the pancreatic tissue , even not completely, but at least regaining the physiological function in the form of improvement ,decrease, of blood glucose level resulting from their homing to pancreatic tissue as detected by flourescent microscopy examination.
On the other hand , it was also found that transplantation of MSCs, although helping to reduce blood glucose and preventing further blood glucose increase in experimental-diabetic rats, is insufficient to restore normoglycemia , as the mean value of blood glucose level was 82.7±6.8 in GI and 86.6±7.4in GII. These values showed a significant increase to reach 248.5±15.5 in GIII, but dropped to reach 134.5±14.2 in GIV.
So, the present study demonstrates the concept that bone marrow mesenchymal stem cells (even undifferentiated MSCs) retains its stamens and potential to induce pancreatic regeneration &/or differentiate into functional β-cells on transplantation & can control blood glucose level in diabetic rats. So, can consequently control the complications of type 1 diabetes. Therefore, MSCs represent a source for cell-based treatment of diabetes mellitus .
Conclusion
Allogeneic MSCs transplantation can reduce blood glucose level in recipient STZ-induced diabetic rats. Two aspects of the observations are remarkable: the ability of MSCs of homing to the pancreas; and the ability of transplanted MSCs to repair the injured pancreas by trans differentiation into insulin-producing cells and/or initiating endogenous pancreatic regeneration by neogenesis of islet of recipient origin, as supported by decrease in fasting blood glucose levels prevention of further rise in blood glucose compared to diabetic rats, in addition to the appearance of many small islets. Mostly were found near the pancreatic ducts that are the source of islets during early development of the pancreas. Also, the islet-like distribution of beta cells detected by flourescent microscopy, in the pancreas of recipient rats.