الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Both liver function and kidney performance, having a bidirectional communication, are reciprocally connected and affected by multiple factors: toxic agents, Schistosomiasis, Hepatitis C Virus (HCV) …etc. Liver fibrosis as a chronic hepatic injury is a fatal disease that can cause biochemical deviation e.g. insulin resistance, reduced albumin synthesis, and reduced cholesterol synthesis. At the present time, transplantation is the only trustworthy treatment concerning end stage of hepatic fibrosis. However, there are many complications associated with transplantation like a shortage of organs and other transplantation complications, which urge researchers to find alternative therapeutic solution. Mesenchymal stem cells help to prevent the fibrotic lesions or enhances liver functions in experimental fibrosis models. This work aimed to study the ability of MSCs isolated from Adipose tissues and differentiated into hepatocyte using liver extract to treat liver fibrosis. and renal dysfunction induced by hepato renal toxic agent (CCl4). This was achieved through 40 male Sprague Dwaley rats, which were divided into 4 groups as follow: group (1): 10 rats were served as a normal control group. group (2): 10 rats were given Intra peritoneal i.p. dose of carbon tetrachloride (CCl4) in olive oil (1ml/Kg) twice a week for 4 weeks to induce fibrosis in the liver. These rats were served as diseased group. group (3): 10 rats were injected with CCl4 as in group 2 and then they were treated with intravenous injection of 3 x 106 cells of AD-MSCs. group (4): 10 rats were injected with CCl4 as in group 2 and then they were given an intravenous injection of differentiated AD-MSCs. This study achieved its aim through the following steps: 1- Isolation of mesenchymal stem cells from rat adipose tissue 2- Culturing of stem cells till passage 3. characterization of AD-MSCs by: Flow cytometery analysis Multilineage differentiation. Differentiation of AD-MSCs with liver extract. Transplantation of isolated ADMSCs in S.D rats After 8 weeks, the blood and liver tissues samples were collected. Biochemical analysis: Determination of serum ALT and AST activities. Determination of serum creatinine. Determination of serum y-Glutamyl Transferase (GGT) Activity. Determination of antioxidant: Lipid peroxide (malondialdehyde (MDA)): Superoxide dismutase (SOD) Catalase assay 11- Gene expression of undifferentiated as well as differentiated cells for specific hepatic genes like hepatocyte nuclear factor 4, alpha fetoprotein and cytokeratin 18 in addition to endogenous reference gene. The results of the present study can be summarized as follow: • Spindle fibroblast shape of mesenchymal stem cells was observed after five days from the isolation step. The confluence of these cells was gradually increased within 10-12 days at which it reached 8090% and the cells were sub-cultured into several passages. • After passage three, the cells were collected to determine the expression level for CD45, CD34, CD 29 and CD44. Flow cytometery results showed that this cells were MSCs due to its positive expression for CD29 (90.66%), CD44 (93.31%) and its negative expression for CD45 (0.16%) and CD34 (0.04%). • Multilineage differentiation proved that our isolated cells had the ability to differentiate into adipocytes, chondrocytes, and osteocytes when the appropriate growth factors were added. These results indicated that relatively purified AD-MSCs were isolated. • The biochemical investigation results for liver function enzymes (AST, ALT, GGT and ALP) showed that the two groups that received 3x106 AD-MSCs had significantly better liver enzymes than diseased group but almost near normal control group. • The antioxidant results proved that the ability of AD-MSCs and differentiated ADMSCs to increase the level of CAT and SOD antioxidant enzymes and decrease MDA free radical enzyme in treated groups than in diseased group in the homogenate tissues. • Histopatholgical examination proved that AD-MSCs and differentiated AD-MSCs showed a remarkable improvement in the hepatocytes as they appeared nearly similar to that of the control rats. Only few hepatocytes appeared with slight vacuolated cytoplasm. • Gene expression of Alpha-fetoprotein (αFP), CK-18, and β-actin S indicated that there was an increasing in expression in the fibrotic tissues and decreasing in AD-MSCs and differentiated ADMSCs transplanted groups while there is marked increasing in COL3- A1 expression in pretreated AD-MSCs transplanted group but it is also slightly increase in AD-MSCs transplanted group. Finally, TGF-ß is markedly increased in pretreated AD-MSCs transplanted group and decrease in other groups.