Dr. Sachin's talk

Aug 05, 2010 - 16:00

Aug 05, 2010 - 17:30

Creativity hall (Room 118) Chemical Eng.

Seminars

Dr. Sachin S. Kadam Research Associate Department of Chemical Engineering IITB.

Abstract Background: In recent years the number of diabetic patients all over the world is increasing rapidly and there is an urgent need to find out alternative sources for the management of diabetes mellitus. Exogenous insulin is used to control hyperglycemia in diabetic patients; however hypoglycemic episodes are unavoidable. Over the last several decades islet transplantation has been developed as a promising method to achieve stringent control of blood glucose and a potential cure for type 1 diabetes. However due to the shortage of donor pancreata alternative sources of islets have been sought through the generation of beta cells from stem cells. Toward that end embryonic stem cells adult tissue-residing progenitor cells and pancreatic duct progenitor cells may serve as sources of islet cell surrogates. Insulin-producing cells generated from stem or progenitor cells display subsets of native islet-cell attributes indicating the need for further development of methods for differentiation to completely functional islets. The ethical and biological limitations with current sources of stem cells resulted in a quest to look for alternative source of multipotent stem cells of human origin. Post natal tissues/membrane is of interest as a source of cells for regenerative medicine because of its ease of availability plasticity and inexhaustible source that does not violate the sanctity of independent life. Encapsulation of these islet like cells in Biocompatible capsule for transplantation in diabetic mice is a novelty of this work.Methods: In present study we have established long-term culture of mesenchymal like stem cells derived from full term human amniotic membrane and their differentiation into functional pancreatic lineage. Results: The post natal mesenchymal like stem cells expressed various mesenchymal markers and also demonstrated multilineage differentiation capacity. Further we observed that these cells can also form islet like clusters (ILC) on exposure to serum free defined media containing specific growth factor and differentiating agents. Differentiated ILCs showed expression of human insulin glucagon and somatostatin by immunocytochemistry while qRT PCR data demonstrate the expression of insulin glucagon somatostatin ngn3 and isl1. Moreover encapsulation of the ILCs in polyurethane polyvinylpyrrolidone macrocapsules and their subsequent transplantation in experimental diabetic mice resulted in restoration of normoglycemia indicating their ability to respond to high glucose without immunorejection. Conclusion: Our results demonstrate that post natal mesenchymal stem cells can undergo islet neogenesis indicating amnion as an alternative source for obtaining islets for cell replacement therapy in diabetes. Encapsulations of these islets into biocompatible macrocapsule open the new door for preparation of bioartificial pancreas for possible diabetes treatment.