Background: Diabetes Mellitus (D.M.) is a major health problem affecting more than 200 million worldwide. The ideal treatment for autoimmune type I diabetes is regeneration of endogenous β-cells which could be achieved by mesenchymal stem cells transplantation. Aim of the work:This work aimed to compare the effect of intravenous bone marrow derived mesenchymal stem cells (BMSCs) and adipose tissue derived mesenchymal stem cells (AMSCs) on Streptozotocin (STZ)-induced type I diabetes in albino rats. Material and Methods: Fifty albino male rats were divided into 4 groups; control, diabetic, BMSCs treated and AMSCs treated. Treated groups were intravenously given 1 ml PKH26 labeled allogenic BMSCs or AMSCs suspended in phosphate buffered saline, respectively. Animals of all groups were sacrificed 2 weeks after stem cells administration. Sections from control and treated groups were examined by fluorescence microscope. Sections from all groups were immunohistochemically stained to detect insulin and proliferating cell nuclear antigen (PCNA). Mean area percent of insulin and number of PCNA positive reactions were measured and statistically analyzed. Results: Diabetic rats showed cell death and congested blood vessels in both exocrine and endocrine pancreas. Treated groups revealed homing of stem cells in pancreas after their transplantation. Moreover, nearly normal histological features were seen in AMSCs treated group. Studying the treated groups immunohistochemically, revealed increase in insulin and PCNA positive reactions when compared to diabetic group with more increase in AMSCs treated group than BMSCs treated group. Conclusion: Intravenous AMSCs could be more effective than BMSCs in treatment of STZ-induced type I diabetes.

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Background and Objectives: The rapidly increasing number of diabetic patients across the world drew the attention to develop more effective therapeutic approaches. Recent investigations on newly differentiated insulin producing cells (IPCs) revealed that they could be derived from embryonic, adult mesenchymal and hematopoietic stem cells. This work was planned to evaluate the role of StemEnhance (Aphanizomenon flos-aquae [AFA] plant extract) in mobilizing naturally occurring bone marrow stem cells as well as in improving streptozotocin-induced diabetic rats. Methods and Results: Twenty adult male albino rats were divided into four groups namely the control, the diabetic, the positive control-StemEnhance and the diabetic-StemEnhance groups. After diabetes induction by streptozotocin (STZ), rats received StemEnhance for four weeks. The mean number of blood CD34 immunopositive cells was measured by flowcytometry and random blood sugar was measured weekly. The pancreas was removed from the sacrificed rats and processed for staining with H&E and immunohistochemical staining for CD34+ve and insulin +ve cells. CD34+ve cells increased in the blood after introduction of StemEnhance. CD34+ve cells were observed in the pancreas and the insulin producing cells in the islets of Langerhans were increased from the second to the fourth week of treatment. Blood glucose level improved but it was still higher than the control level after four weeks of StemEnhance treatment. Conclusions: This work points to the significant role of StemEnhance in stem cell mobilization and the improvement of diabetes mellitus.

Introduction: Ulcerative colitis (UC) is a chronic inflammatory condition characterized by acute episodes of colonic inflammation. Its pathogenesis is associated with decreased antioxidant capability. Royal Jelly (RJ) is usually used as a complementary therapy in various diseases because of its antioxidant, anti-inflammatory and immunomodulatory effects. Aim of the work:To evaluate the protective effect of RJ against acetic acid-induced UC in adult male albino rats. Materials and Methods: Thirty rats were divided equally into 3 groups. Group I was the control group. Group II included rats subjected to intracolonic acetic acid (AA) for induction of UC. Group III 10 rats treated with RJ (250 mg/kg/day orally) for 7 days, thereafter subjected to AA. RJ was administered for another 14 days. Rats were sacrificed after 21 days. Serum glutathione (GSH) and malondialdehyde (MDA) were assessed. Colonic sections were subjected to H&E, Periodic Acid Schiff (PAS), toluidine blue, Mallory's trichrome stains and cyclooxygenase-2 (COX-2) immunohistochemical stain. Results: Group II showed significant decrease in GSH, significant increase in MDA and marked histological alterations in colon. There was a significant decrease in the number of goblet cells, but significant increases in the number of mast cells, area% of collagen fibers and COX-2 immunoexpression compared to the control. In group III, GSH was significantly increased and MDA was significantly decreased compared to group II. The colon showed minimal changes, significant increase in the number of goblet cells, significant reduction in the number of mast cells, collagen deposition and COX-2 immunoreactivity compared to group II. When compared to the control, there was no significant difference regards the serological, histological and morphometric results, except for the number of goblet cells that revealed significant decrease. Conclusion: RJ proven to protect against acetic acid-induced UC in albino rats.

Background and Objectives:Depression is one of the most prevalent psychiatric disorders. Endogenous neural stem cells (NSCs) could replace damaged Hippocampal neurons in depression. This work was planned to evaluate Rhodiola rosea (Rr) extract possible role in stimulation of NSCs proliferation and in depression improvement.Methods and Results:Thirty adult male albino rats were divided into three groups; control, untreated depressed model and Rr model. After depression induction by chronic mild stress, rats received Rr extract 1.5 g/kg/day for three weeks. The sucrose preference test (SP) was done before, after depression induction and 3 weeks after supplementation of Rr. The brain was removed and processed for H&E and immunohistochemical staining for caspase 3, glial fibrillary acid protein (GFAP) and proliferating cell nuclear antigen (PCNA). Rr group revealed improved sucrose preference, increased undamaged neurons and decreased dark neurons. Moreover, Caspase 3 +ve cells were not detected, GFAP +ve cells increased and PCNA +ve cells were detected only in Rr group.Conclusions:This work points to the role of Rr in depression improvement and in stimulation of NSCs proliferation.

Introduction: Sepsis is a major health problem with high mortality rate, despite advanced medications. Although hypothalamic-pituitary-adrenal (HPA) axis activation can control its destructive inflammatory reactions, adrenal insufficiency (AI) is commonly associated with it. Mesenchymal Stem Cell-Derived Microvesicles (MSCs-MVs) were proved to be as effective as their origin cells in tissue repair. Aim of the work: To study the effects of Escherichia coli-lipopolysaccharides (E. coli-LPS) induced sepsis on Zona fasciculata of adult male albino rats and probable therapeutic effects of adipose derived mesenchymal stem cells-microvesicles (ADMSCs-MVs). Materials and Methods: Forty-four adult male albino rats were divided into three groups; (I) the controls, (II) LPS and (III) MV. Sepsis was induced in LPS and MV-groups using E. coli-LPS. Four hours later, MV-group received single intravenous (IV) injection of PKH26 labelled ADMSCs-MVs. All animals were sacrificed 48 hours after ADMSCs-MVs administration. Tumor necrosis factor-α (TNF-α), cyclo-oxygenase-2 (COX-2) and nitric oxide (NO) levels were measured in adrenal homogenates of each group. Sections from all groups were subjected to H&E, besides, immunohistochemical stains for CD44, inducible nitric oxide synthase (iNOS) and proliferating cell nuclear antigen (PCNA). Unstained sections of subgroup IC and MV-group were examined by fluorescent microscope. Mean number of CD44 and PCNA positive cells and mean area percent of iNOS immunoreaction were measured and data were statistically analyzed. Results: LPS-group showed non-survivors (24 hours after LPS-injection) and survivors with features of Zona fasciculata inflammatory damage, besides increased TNF-α and NO and decreased COX-2. The MV-group revealed marked increase in CD44 and PCNA, but significant decrease in iNOS immunoreactions. Additionally, ADMSCs-MV homing was detected in Zona fasciculata. Conclusion: LPS-induced sepsis caused marked Zona fasciculata inflammatory degeneration improved by ADMSCs-MVs single IV injection; mostly through transfer of proteins, mRNA, microRNA and/or organelles with reparative functions from ADMSCs to the injured tissues.

Background: Ischemia/reperfusion injury (IRI) is a foremost reason for acute kidney injury, which is a common clinical complication having high morbidity rate and lacks effective therapy. Renin-angiotensin system (RAS) activation and angiotensin II level elevation are important risk factors in IRI. Aliskiren (ALS) is the first oral direct rennin inhibitor that blocks the first step in RAS and has been approved for treating hypertension. Aim of work: Investigating whether ALS pretreatment protects the renal cortex of adult male albino rats subjected to IRI. Material and Methods: Thirty adult male albino rats were divided into 3 groups: group I (control group), group II (IRI group): were subjected to IRI procedure, group III (ALS group): rats were pretreated with aliskiren (ALS, 100 mg/kg) twice orally 24h and 1h before IRI and left for 24h of reperfusion before scarification. Blood samples were taken to estimate the levels of blood urea nitrogen (BUN), serum creatinine (SCr) and superoxide dismutase enzyme (SOD). Kidneys sections were stained with HandE and PAS stains and immunohistochemical staining against COX-2 and caspase-3. This was followed by morphometric and statistical analysis. Results: IRI group showed deterioration in renal function tests with massive histological alterations in the Malpighian renal corpuscles and the convoluted tubules. There was significant decrease in optical density of PAS reaction, with significant increase in the mean area% of COX-2 and caspase-3 immunoexpression. ALS group showed significant improvement in renal function tests with preserved normal histology of the renal cortex. There was significant increase in the optical density of PAS reaction, with significant decrease in the mean area% of COX-2 and caspase-3 immunoexpression. Conclusion:A protective effect of ALS was detected in IRI-induced renal cortical damage in adult male albino rats. This was evidenced by laboratory results, histological and immunohistochemical evaluation.

Background: Skin is the largest protective organ in the body, but it is frequently injured by either acute or chronic wounds. Prolonged healing and scar formation are two major challenges in treating wounds, resulting in physical, mental and socioeconomic burden to the affected subjects. Exosomes (Exos) are naturally secreted vesicles playing a vital role in the transfer of RNA to neighboring or distant recipient cells and there are numerous on-going studies on their role of in tissue regeneration and wound healing. Aim of the work: Evaluation of the efficiency of Exos derived from adipose stem cells on cutaneous wound healing in adult male albino rats. Materials and Methods: Thirty-four rats were divided into three groups; Group I: control. Group II: a dorsal cut wound (1.5 × 1.5 cm) was done to each rat. Group III: the same wound was done and rats were injected with 200μ PKH26-labeled Exos intravenously. Rats were sacrificed after 21 days. Skin sections were subjected to hematoxylin and eosin (HandE), Mallory's trichrome and orcein stains, alpha smooth muscle actin (α-SMA) and Ki67 immunohistochemical stains. Results: Skin sections from group II showed scar formation, lost epidermal layers and hair follicles. There was significant increase in collagen fibers and α-SMA immunoreaction, with significant decrease in elastic fibers and Ki67 immunoexpression compared to the control. In group III, the skin revealed almost normal histology, significant decrease in collagen fibers and α-SMA, with significant increase in elastic fibers and Ki67 immunoreaction compared to group II. Conclusion: Exos injection has demonstrated a beneficial effect on cutaneous wound healing and could prevent scar formation in adult male albino rats.