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- W4319999999 abstract "Diabetes is a long-standing disease with increasing prevalence that contributes to significant health care costs and patient morbidity. Over the last 100 years, since the discovery of insulin by Banting and Best, the primary treatment has remained subcutaneous insulin delivery. Although novel insulin formulations, glycemic measurement techniques, and delivery methods have been developed, complications remain common and a cure is desperately required. Understanding the pathophysiology and cellular mechanisms of autoimmunity driving diabetes is key to engineering a cure for this important disease. Islet cell transplantation has evolved over the last 20 years as an attempt to disease cure and has now reached nearly 50% success rates due to improved understanding and management of the alloimmune and autoimmune response following implantation. However, limited cadaveric supply and ongoing immune barriers has led to the development of novel islet cell transplant via inducible pluripotent stem cells (iPSC). This novel therapy offers unlimited supply and multiple unique solutions for alloimmune control. Autologous iPSC-based islet cell transplant may resolve alloimmune concerns but requires expensive and time-consuming personalized medicine. Meanwhile, allogeneic iPSC-based islet cell transplant may enable HLA-matched transplant with less cost and time requirements but has persistent autoimmune and alloimmune barriers. Genetic modifications with CRISPR/Cas9 techniques could theoretically provide immune silenced or immune protected iPSCs for islet cell transplant but this requires further trials to strengthen the evidence. Parallel studies continue to evaluate the utility of diabetes reversal with immune reset. Clinical trials are ongoing evaluating the efficacy of resetting the immune system at the onset of diabetes to eliminate autoimmunity and prolong insulin free periods for patients. Combining these techniques with allogeneic or HLA-matched iPSC-based islet cell transplant provides a bright future for diabetes treatment and cure. This chapter discusses drawbacks of historic subcutaneous insulin treatment methods, novel continuous glucose monitoring, continuous subcutaneous insulin infusion (CSII, i.e., insulin pump), and closed-loop wearable insulin delivery (i.e., artificial pancreas) devices. We review our current understanding of the physiologic function and microstructure of islet cells, pathophysiology of diabetes, and current islet cell transplant methods including the autoimmune approach. We also discuss future directions for advancement including iPSC-based islet cell transplant (isogeneic versus allogeneic), genetically modified iPSC therapies, and immune reset trials." @default.
- W4319999999 created "2023-02-11" @default.
- W4319999999 creator A5048882927 @default.
- W4319999999 creator A5067408895 @default.
- W4319999999 date "2023-01-01" @default.
- W4319999999 modified "2023-09-30" @default.
- W4319999999 title "The potential of cellular transplantation to harness autoimmunity and reverse clinical diabetes" @default.
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