Islet Regeneration during the Reversal of Autoimmune Diabetes in NOD Mice

• Published in: Science (American Association for the Advancement of Science) 2003-11, Vol.302 (5648), p.1223-1227
• Main Authors: Kodama, Shohta, Kühtreiber, Willem, Fujimura, Satoshi, Dale, Elizabeth A., Faustman, Denise L.
• Format: Article
• Language: English
• Subjects: Animals; Autoimmunity; B lymphocytes; Biological and medical sciences; Blood Glucose - analysis; Cell Differentiation; Cell Fusion; Cell Transplantation; Combined Modality Therapy; Comparative analysis; Diabetes; Diabetes complications; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - pathology; Diabetes Mellitus, Type 1 - physiopathology; Diabetes Mellitus, Type 1 - therapy; Diabetes. Impaired glucose tolerance; Donors; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Epithelial cells; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Exocrine cells; Female; Females; Freund's Adjuvant - therapeutic use; Immunology; In Situ Hybridization, Fluorescence; Insulin - analysis; Islet cells; Islets of Langerhans - pathology; Islets of Langerhans - physiology; Islets of Langerhans Transplantation; Leukocyte Common Antigens - analysis; Male; Medical sciences; Mice; Mice, Inbred NOD; Pancreas; Pancreatic Ducts - cytology; Ploidies; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Proteins; Regeneration; Sex chromosomes; Spleen - cytology; Spleen - radiation effects; Splenocytes; Stem Cells - physiology; T lymphocytes; Type 1 diabetes
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1088949

Nonobese diabetic (NOD) mice are a model for type 1 diabetes in humans. Treatment of NOD mice with end-stage disease by injection of donor splenocytes and complete Freund's adjuvant eliminates autoimmunity and permanently restores normoglycemia. The return of endogenous insulin secretion is accompanied by the reappearance of pancreatic β cells. We now show that live donor male or labeled splenocytes administered to diabetic NOD females contain cells that rapidly differentiate into islet and ductal epithelial cells within the pancreas. Treatment with irradiated splenocytes is also followed by islet regeneration, but at a slower rate. The islets generated in both instances are persistent, functional, and apparent in all NOD hosts with permanent disease reversal.