Current Concepts of Using Pigs as a Source for Beta-Cell Replacement Therapy of Type 1 Diabetes

Abstract

The global prevalence of insulin-dependent diabetes mellitus is rapidly increasing. In spite of major improvements in insulin treatment regimens and diabetes technology (e.g., artificial pancreas devices), glucose control remains problematic in a substantial proportion of diabetic patients. Those patients may benefit from beta-cell replacement therapies. Allotransplantation of pancreas or isolated pancreatic islets is limited by the small number of organ donors. Thus, alternative sources of beta-cells are being developed and tested. These include endocrine progenitor cells or mature beta-cells derived from pluripotent human stem cells and attempts to derive human pancreas tissue in animal hosts by interspecific chimeric complementation experiments. Xenotransplantation of porcine islets is a realistic alternative option. Immune rejection of xenoislets can be prevented by immunosuppression of the recipient or by encapsulation of the islets in microdevices or macrodevices. Using precise and efficient genetic engineering of donor pigs, immune-protected xenoislets with improved functionality can be generated.

Animal models of obesity and diabetes mellitus

“…insulin-dependent diabetes mellitus 338,339 or as a source of reporter islets for ex vivo studies of β-cell maturation, proliferation and heterogeneity 340 . While pigs are increasingly used as models for obesity and diabetes mellitus research, dogs remain an important model in this field, particularly for studies involving oral administration of compounds, which is much easier in dogs than in pigs (TABLE 3).…”

Production of high‐quality islets from goettingen minipigs: Choice of organ preservation solution, donor pool, and optimal cold ischemia time

“…32 Besides the use of porcine organs other alternative sources for beta cell replacement therapy are highly debatable and intensely investigated. 33 Porcine organs are of course in focus of being a potentially unlimited source [1][2][3]34 and a suitable option due to the short genetic distance to man and physiological similarity. Furthermore, pigs bring the advantage of the possibility for genetic modification, 33 as new technologies allow for tailored genome modifications aiming for increasing safety and efficacy of porcine derived islets.…”

Optimization of nano-encapsulation on neonatal porcine islet-like cell clusters using polymersomes

“…Often, neonatal porcine islet-like cell clusters (NPCCs) are preferred over adult porcine islets (APIs) owing to their affordability and ease of isolation. In addition, NPCCs can proliferate gradually after transplantation, prolonging their function in vivo [1,2].. However, when NPCCs are transplanted into human or non-human primate (NHP) portal veins, interspecies variations can cause immune reactions such as instant blood-mediated in ammatory reaction (IBMIR) or hyperacute rejection, leading to early graft loss [3].…”