ABSTRACT
End-stage liver disease is a worldwide cause of morbidity and mortality, which is associated with a considerable economic burden. As the disease progresses, fibrosis will replace the hepatic architecture and compromise liver functions. The regenerative approach for the injured liver can provide a hope for these patients; however, it is still facing many challenges. In the current study, we aimed at (1) assessing hepatic regenerative capacity of mesenchymal stem cells, isolated from human umbilical cord blood (HMSCs), in a rat model of carbon-tetrachloride (CCL4) induced liver fibrosis, (2) comparing the therapeutic effects with other cell populations derived from umbilical cord blood and (3) evaluating the host response to the human-derived cells. Fifteen rats received either the whole mononuclear cell fraction (HMNCs), CD34-ve subpopulation or HMSCs. A fourth group did not receive any treatment and another group was left without induction of fibrosis as positive and negative controls. All groups that received cellular treatment showed homing of the human cells and improvement of the liver architecture and functional capacity. The groups received CD34-ve cells and HMSCs had the most efficient improvement in liver functions, microscopic regenerative markers and histological appearance while the least immune reaction was noted with HMSCs. HUCB-MSCs showed significant immunemodulatory effect on rat immune cells. This study can provide a clue about a simple and effective method for the management of fibrotic liver diseases.
ABSTRACT
INTRODUCTION: Recent studies have demonstrated remote effects of renal ischemia/reperfusion (IR) injury on some organs such as brain, liver, and lungs. Oxidative stress is reported to be the cornerstone in such ischemic conditions. Associated apoptosis is also reported in remote lung, liver and myocardial injury after acute kidney injury. So, we postulated that renal IR may affect the pancreas by its remote effect. Oxidative stress and mitochondrial mediated apoptosis may play a crucial role in this injury. We investigated the effects of kidney IR on pancreatic exocrine and endocrine functions, antioxidant enzyme activity, and apoptosis. MATERIAL AND METHODS: The protective effect of vitamin C was also investigated. The animals were submitted to non-traumatic bilateral renal IR, sham operation or treatment with vitamin C after IR. Rats were sacrificed on the 1(st), 3(rd), and 7(th) days of the experiment to evaluate the parameters of oxidative stress (catalase, lipid peroxidase, reduced glutathione and superoxide dismutase), pancreatic endocrine and exocrine function (amylase, insulin and fasting blood glucose), renal functions (serum creatinine and blood urea nitrogen), cellular injury and apoptotic markers (Bcl-2, Bax and caspase-3). RESULTS: Kidney I/R significantly increased the renal and pancreatic functions at 1, 3 and 7 days, while fasting insulin was significantly increased at day 3 after ischemia. Moreover, I/R significantly increased the studied oxidative stress markers and decreased the antioxidant capacity in pancreatic tissues. In addition, renal I/R induced numerous histopatological lesions in pancreatic tissues and increased the apoptosis-related genes. Treating the rats with vitamin C (100 mg/kg) significantly restored the renal and pancreatic functions, improved the pancreatic antioxidant capacity and protected the pancreatic tissues from apoptotic necrosis. CONCLUSIONS: The results suggested that bilateral renal ischemia for 45 min caused significant impairment of pancreatic function and structure as indicators of acute pancreatitis. While IR enhances oxidative stress and apoptosis, vitamin C appears to play a cytoprotective role.
