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Differentiation of Pancreatic Ductal Epithelial Cells into Insulin Like Cell Clusters in Chronic Pancreatitis

Open Journal of Endocrine and Metabolic Diseases 2015年第12期5卷 177-183页

作者： pondugala pavan kumar Gaddipati Radhika G. Venkat Rao D. Nageshwar Reddy M. Sasikala Asian Health Care Foundation Somajiguda Hyderabad India Asian Institute of Gastroenterology Somajiguda Hyderabad India

Background/Aim: Islet regeneration in chronic pancreatitis (CP) is relevant for managing the associated loss of endocrine function. Because ductal epithelial cells were earlier demonstrated to differentiate into pancreatic endocrine mass, we evaluated their proliferation and differentiation in chronic pancreatitis. Methods: Pancreatic ducts were obtained from surgically resected pancreata of 12 patients with chronic pancreatitis and 15 control subjects. CK19 positive ductal cells were evaluated for their proliferating and differentiating abilities upon immunostaining with Ki 67 and hormone positivity for insulin and glucagon, apart from monitoring Pdx 1 expression. Results: In comparison to the controls, a greater number of proliferating pancreatic ductal epithelial cells (PDECs) were observed under conditions of CP. The increase in Pdx1 expressing PDECs (22%) and proliferating Pdx1 expressing PDECs (30%) was significant (P < 0.04). Number of cells expressing insulin/glucagon in the exocrine ducts increased significantly in CP as compared to controls (P ?β?cell mass adjacent to the ducts increased by 28%.?Conclusion: Enhanced capability of PDECs to proliferate and differentiate into endocrine mass suggests that PDECs form a source of progenitors for cell based therapy in chronic pancreatitis.

关键词： Chronic Pancreatitis Ductal Epithelial Cells Islet Like Clusters Cell Differentiation

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Dietary Green Tea Extract and Antioxidants Improve Insulin Secretory Functions of Pancreatic β-Cells in Mild and Severe Experimental Rodent Model of Chronic Pancreatitis

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Open Journal of Endocrine and Metabolic Diseases 2024年第2期14卷 53-72页

作者： Galande Sheethal Ranjeet K. Tokala pavan pondugala Krishna Vemula Vijayalakshmi Venkatesan Pothani Suresh Surya Satyanarayana Singh Guduru Venkat Rao Duvvur Nageshwar Reddy Mitnala Sasikala Basic Science and Translational Research Division Asian Healthcare Foundation AIG Hospitals Hyderabad India Division of Cell and Molecular Biology National institute of Nutrition Hyderabad India National Animal Resource Facility for Biomedical Research Hyderabad India Department of Biochemistry Osmania University Hyderabad India Department of Surgical Gastroenterology Asian Institute of Gastroenterology Hyderabad India Department of Gastroenterology Asian Institute of Gastroenterology Hyderabad India

Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. It is predominantly idiopathic (with an unknown cause) in India and mostly due to alcohol in the West. Diabetes that occur secondary to chronic pancreatitis (T3c Diabetes) is often brittle, and is difficult to attain normoglycemia with conventional treatment requiring multiple doses of insulin. Mild and severe model of CP was induced in mice by repeated intraperitoneal injections of cerulein and L-arginine respectively with an intent to study islet dysfunction and develop therapeutic strategy in animal models of CP. Dietary intervention of epigallocatechin-3-gallate (EGCG) was tested in both the models of CP for its beneficial effects on insulin secretory functions. Pancreata collected upon euthanasia were used to study alterations in the morphology of pancreatic parenchyma and inflammation by staining with H&E and fibrotic changes by Masson’s trichrome and picrosirius staining. Insulin secretory functions of islets were evaluated to test the efficacy of the dietary intervention on β-cell functions. Intraperitoneal glucose tolerance test was performed to monitor the glucose homeostasis before and after the dietary intervention. Both the models resulted in CP with dispersed acini, inflammation and fibrosis. The loss of acini and extent of fibrosis was more in L-arginine model. 2-fold improvement in glucose-stimulated insulin secretory functions of islets was observed with 0.5% EGCG dietary intervention in cerulein model of CP and 1.6-fold in L-arginine model of CP. A further improvement in insulin secretion by 3.2-fold was observed with additional dietary supplements like N-acetyl cysteine, curcumin in combination with EGCG. Our results thus demonstrate and highlight the therapeutic potential of dietary green tea (EGCG) supplementation in reversing islet dysfunction and improving glucose homeostasis in experimental chronic pancreatitis in mice.

关键词： Dietary Intervention C57BL6/J Mice Epigallocatechin-3-Gallate N-Acetyl Cysteine Curcumin Chronic Pancreatitis Islets Glucose Stimulated Insulin Secretion

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Identification of circulating CD90^+ CD73^+ cells in cirrhosis of liver

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World Journal of Stem Cells 2011年第7期3卷 63-69页

作者： Mitnala Sasikala Pugazhelthi Surya Gaddipati Radhika pondugala pavan kumar Mekala Subba Rao Rathindra Mohan Mukherjee Padaki Nagaraja Rao D Nageshwar Reddy Institute of Basic Sciences and TranslationalResearch Asian Health Care Foundation Asian Institute of Gastroenterology

AIM:To identify circulating CD90 + CD73 + CD45 cells and evaluate their in vitro proliferating ***:Patients with cirrhosis(n=43),and healthy volunteers(n=40)were recruited to the *** cells were isolated and cultured from the peripheral blood of controls and cirrhosis ***-like cells that appeared in cultures were analyzed for morphological features,enumerated by flow cytometry and confirmed by immunocytochemistry(ICC).Colony forming efficiency(CFE)of these cells was assessed and expressed as a ***:In comparison to healthy volunteers,cells obtained from cirrhotic patients showed a significantincrease(P<0.001)in the percentage of CD90+CD73+ CD45 cells in *** cells also showed 10 fold increases in *** cytometry and ICC confirmed that the proliferating cells expressed CD90 + CD73 + in the cultures from cirrhosis ***:These results indicate the presence of circulating CD90 + CD73 + CD45 cells in patients with liver cirrhosis that have the potential to proliferate at a higher rate.

关键词： CD90+ CD73+ CD45 cells Liver cirrhosis Proliferation Colony forming efficiency

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