Intrapleural transplantation of allogeneic pancreatic islets achieves glycemic control in a diabetic non-human primate. 2022

Ji Lei, and Alexander Zhang, and Hongping Deng, and Zhihong Yang, and Cole W Peters, and Kang M Lee, and Zhenjuan Wang, and Ivy A Rosales, and Charles G Rickert, and James F Markmann
Center for Transplantation Science, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Clinical islet transplantation has relied almost exclusively on intraportal administration of pancreatic islets, as it has been the only consistent approach to achieve robust graft function in human recipients. However, this approach suffers from significant loss of islet mass from a potent immediate blood-mediated inflammatory response (IBMIR) and a hypoxic environment. To avoid these negative aspects of the portal site, we explored an alternative approach in which allogeneic islets were transplanted into the intrapleural space of a non-human primate (NHP), treated with an immunosuppression regimen previously reported to secure routine survival and tolerance to allogeneic islets in NHP. Robust glycemic control and graft survival were achieved for the planned study period of >90 days. Our observations suggest the intrapleural space provides an attractive locale for islet transplantation due to its higher oxygen tension, ability to accommodate large transplant tissue volumes, and a lack of IBMIR-mediated islet damage. Our preliminary results reveal the promise of the intrapleural space as an alternative site for clinical islet transplantation in the treatment of type 1 diabetes.

UI MeSH Term Description Entries
D007515 Islets of Langerhans Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN. Islands of Langerhans,Islet Cells,Nesidioblasts,Pancreas, Endocrine,Pancreatic Islets,Cell, Islet,Cells, Islet,Endocrine Pancreas,Islet Cell,Islet, Pancreatic,Islets, Pancreatic,Langerhans Islands,Langerhans Islets,Nesidioblast,Pancreatic Islet
D011323 Primates An order of mammals consisting of more than 300 species that include LEMURS; LORISIDAE; TARSIERS; MONKEYS; and HOMINIDS. They are characterized by a relatively large brain when compared with other terrestrial mammals, forward-facing eyes, the presence of a CALCARINE SULCUS, and specialized MECHANORECEPTORS in the hands and feet which allow the perception of light touch. Primate
D003922 Diabetes Mellitus, Type 1 A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence. Diabetes Mellitus, Brittle,Diabetes Mellitus, Insulin-Dependent,Diabetes Mellitus, Juvenile-Onset,Diabetes Mellitus, Ketosis-Prone,Diabetes Mellitus, Sudden-Onset,Diabetes, Autoimmune,IDDM,Autoimmune Diabetes,Diabetes Mellitus, Insulin-Dependent, 1,Diabetes Mellitus, Type I,Insulin-Dependent Diabetes Mellitus 1,Juvenile-Onset Diabetes,Type 1 Diabetes,Type 1 Diabetes Mellitus,Brittle Diabetes Mellitus,Diabetes Mellitus, Insulin Dependent,Diabetes Mellitus, Juvenile Onset,Diabetes Mellitus, Ketosis Prone,Diabetes Mellitus, Sudden Onset,Diabetes, Juvenile-Onset,Diabetes, Type 1,Insulin Dependent Diabetes Mellitus 1,Insulin-Dependent Diabetes Mellitus,Juvenile Onset Diabetes,Juvenile-Onset Diabetes Mellitus,Ketosis-Prone Diabetes Mellitus,Sudden-Onset Diabetes Mellitus
D006085 Graft Survival The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. Graft Survivals,Survival, Graft,Survivals, Graft
D000085002 Glycemic Control Strategies used for regulating BLOOD GLUCOSE levels. Such strategies include administration of INSULIN; DIETARY MODIFICATION; and EXERCISE. Blood Glucose Control,Control, Blood Glucose,Control, Glycemic,Glucose Control, Blood
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016381 Islets of Langerhans Transplantation The transference of pancreatic islets within an individual, between individuals of the same species, or between individuals of different species. Grafting, Islets of Langerhans,Pancreatic Islets Transplantation,Transplantation, Islets of Langerhans,Transplantation, Pancreatic Islets,Islands of Langerhans Transplantation,Islands of Pancreas Transplantation,Islet Transplantation,Transplantation, Islands of Langerhans,Transplantation, Islands of Pancreas,Transplantation, Islet,Islet Transplantations,Islets Transplantation, Pancreatic,Transplantations, Islet
D018380 Hematopoietic Stem Cell Transplantation Transfer of HEMATOPOIETIC STEM CELLS from BONE MARROW or BLOOD between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). Hematopoietic stem cell transplantation has been used as an alternative to BONE MARROW TRANSPLANTATION in the treatment of a variety of neoplasms. Stem Cell Transplantation, Hematopoietic,Transplantation, Hematopoietic Stem Cell

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