Abstract
Islet transplantation is an attractive treatment of type 1 diabetes mellitus (T1DM). Animal models of diabetes mellitus (DM) contribute a lot to the experimental studies of islet transplantation and to evaluations of isolated islet grafts for future clinical applications. Diabetic nonhuman primates (NHPs) represent the suitable models of DMs to better evaluate the effectiveness of islet transplantation, to assess new strategies for controlling blood glucose (BG), relieving immune rejection, or prolonging islet survival, and eventually to translate the preclinical data into tangible clinical practice. This review introduces some NHP models of DM, clarifies why and how the models should be used, and elucidates the usefulness and limitations of the models in islet transplantation.
Highlights
Type 1 diabetes mellitus (T1DM), once known as insulindependent diabetes mellitus (IDDM), is an autoimmune disorder caused by progressive destruction of insulin-producing pancreatic β-cell that results in hyperglycemia [1, 2]
Rigorous trial test of the islet grafts from various sources on preclinical large animal models of DM represents an important step to better verify the effectiveness of islet transplantation and develop novel approaches for T1DM treatment
We introduce some nonhuman primates (NHPs) models of DM, clarify why and how the models should be used, and elucidate the usefulness and limitations of the models in islet transplantation
Summary
Type 1 diabetes mellitus (T1DM), once known as insulindependent diabetes mellitus (IDDM), is an autoimmune disorder caused by progressive destruction of insulin-producing pancreatic β-cell that results in hyperglycemia [1, 2]. Journal of Diabetes Research islet transplant research safely into tangible clinical applications due to advantages including (1) evolutionary proximity to human beings, with approximately 95% of homology at the nucleotide level [29]; (2) similar clinical features of diabetes between NHPs and humans [30,31,32,33]; (3) the fact that large body size and long lifespan of NPHs make it possible and convenient to perform longitudinal studies and numerous procedures (e.g., biopsy of pancreatic tissues, extraction of large volumes of blood samples, or surgical implantation of catheters) [34]; and the fact that (4) immune system of NHPs closely resembles that of humans, making it possible and useful to study immunological aspects related with islet transplantation, as well as to develop and verify strategies to improve islet graft survival for future clinical practice Another important requirement for preclinical test in NHPs is based on the indefinite translation of rodent protocols to outbred NHPs. Even though numerous protocols are effectively applied to induce immune tolerance in rodent models, only a small amount of strategies can prolong rejection-free interval (RFI) survival without sustained severe immunosuppressive treatment in NHP models [35]. We introduce some NHP models of DM, clarify why and how the models should be used, and elucidate the usefulness and limitations of the models in islet transplantation
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