title: The reversal of diabetes in rat model using mouse insulin producing cells - a combination approach of tissue engineering and macroencapsulation.
abstract: Type 1 diabetes is a chronic disorder resulting from the autoimmune destruction of insulin-producing cells, a leading cause of morbidity and mortality all over the world. In this study a tissue engineering approach was compared with a macroencapsulation approach to reverse type 1 diabetes in a rat model, using mouse pancreatic progenitor cell (PPC)-derived islet-like clusters and mouse islets. For the tissue engineering approach the cells were cultured on gelatin scaffolds cross-linked with EDC in the presence of polyvinylpyrrolidone in vitro (GPE scaffolds), while for the macroencapsulation approach the cells were encapsulated in polyurethane-polyvinylpyrrolidone semi-interpenetrating networks. In the combination approach the cells cultured on GPE scaffolds were further encapsulated in a polyurethane-polyvinylpyrrolidone capsule. Real time PCR studies and the glucose challenge assay have shown that cells on GPE scaffolds could express and secrete insulin and glucagon in vitro. However, under in vivo conditions the animals treated by the tissue engineering approach died within 15-20 days and showed no reversal of their diabetes, due to infiltration of immune cells such as CD4 and CD8 cells and macrophages. In the macroencapsulation approach the animals showed euglycemia within 25 days, which was maintained for further 20 days, but after that the animals died. Interestingly, in the combination approach the animals showed reversal of hyperglycemia, and remained euglycemic for up to 3 months. The time needed to achieve initial euglycemia was different with different cell types, i.e. the combination approach with mouse islets achieved euglycemia within 15 days, whereas with PPC-derived islet-like clusters euglycemia was achieved within 25 days. This study confirmed that a combination of tissue engineering and macroencapsulation with mouse islets could reverse diabetes and maintain euglycemia in an experimental diabetes rat model for 90 days.
authors.affiliation: Division for Tissue Engineering and Regeneration Technologies, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.
authors.forename: Sudhakar
authors.initials: S
authors.lastname: Muthyala
authors.forename: V R Rana
authors.initials: VR
authors.lastname: Raj
authors.forename: Mira
authors.initials: M
authors.lastname: Mohanty
authors.forename: P V
authors.initials: PV
authors.lastname: Mohanan
authors.forename: Prabha D
authors.initials: PD
authors.lastname: Nair
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000628:therapy*; D004195:Disease Models, Animal; D005215:Fasting / Q000097:blood; D005780:Gelatin; D005786:Gene Expression Regulation / Q000187:drug effects; D005934:Glucagon / Q000235:genetics / Q000378:metabolism; D005951:Glucose Tolerance Test; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000473:pathology / Q000637:transplantation*; D016381:Islets of Langerhans Transplantation; D051379:Mice; D008855:Microscopy, Electron, Scanning; D011140:Polyurethanes / Q000494:pharmacology; D011205:Povidone / Q000494:pharmacology; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014022:Tissue Survival / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011140:Polyurethanes; D005780:Gelatin; D005934:Glucagon; D011205:Povidone