Inducible Pluripotent Stem Cells as a Potential Cure for Diabetes

Abstract

Over the last century, diabetes has been treated with subcutaneous insulin, a discovery that enabled patients to forego death from hyperglycemia. Despite novel insulin formulations, patients with diabetes continue to suffer morbidity and mortality with unsustainable costs to the health care system. Continuous glucose monitoring, wearable insulin pumps, and closed-loop artificial pancreas systems represent an advance, but still fail to recreate physiologic euglycemia and are not universally available. Islet cell transplantation has evolved into a successful modality for treating a subset of patients with ‘brittle’ diabetes but is limited by organ donor supply and immunosuppression requirements. A novel approach involves generating autologous or immune-protected islet cells for transplant from inducible pluripotent stem cells to eliminate detrimental immune responses and organ supply limitations. In this review, we briefly discuss novel mechanisms for subcutaneous insulin delivery and define their shortfalls. We describe embryological development and physiology of islets to better understand their role in glycemic control and, finally, discuss cell-based therapies for diabetes and barriers to widespread use. In response to these barriers, we present the promise of stem cell therapy, and review the current gaps requiring solutions to enable widespread use of stem cells as a potential cure for diabetes.

Characterization and reduction of non-endocrine cells accompanying islet-like endocrine cells differentiated from human iPSC

“…Based on the results of the in vivo experiments, the risk of contaminating non-endocrine cells was relatively low in iPIC. However, considering the cell number (> 1 × 10 8 ) assumed to be needed for implantation in patients 14 , it is reasonable to pursue an understanding of, and methods for reducing, potentially contaminating cells as much as possible, to minimize future clinical risk levels. To expose potentially contaminating non-endocrine cells, we profiled the single-cell transcriptomes of iPIC.…”

“…Given that > 1 × 10 8 cells are used for current islet transplantation protocols 14 , a similar number of cells is assumed to be required for iPSC/ESC-derived pancreatic islet-like cells. Feasible candidate approaches to reduce the number of unintended cells from over hundred million in vitro-generated cells include compound treatments or metabolic selection based on properties specific to the relevant cells.…”

Study on the TCM Syndromes Evolution and Chinese Herbal Characteristics of Type 2 Diabetes Patients with Different Courses of Disease in TCM “Heat Stage”: A Real-World Study

“…For this chronic disease, portraying "cure of diabetes" as a goal for all persons with diabetes, however, is misleading and has the potential to do harm [39]. Even for insulin, it is not a cure for diabetes; it is just a treatment [40]. Standards of Medical Care in Diabetes-2020 [41] mentioned the following: " e goals of treatment for diabetes are to prevent or delay complications and optimize quality of life.…”

Making human pancreatic islet organoids: Progresses on the cell origins, biomaterials and three-dimensional technologies

“…Although efforts have been underway to form a timing closed-loop system by combining insulin pumps with continuous glucose monitors, under a computer algorithm controlling, it still fails to recreate physiologic euglycemia. Hypoglycemia occurs in 31-41% of diabetic patients and this risk escalates with intensive insulin therapy and improved control of hyperglycemia 5 . Therefore, the transplantation of isolated pancreatic islets becomes an alternative for diabetes treatment.…”

“…In this study, islet transplantation was effective with 62.5% of patients achieving the primary endpoint of freedom from severe hypoglycemic events and median HbA1c declined from 8.1% before to 6.0% at 1-year and 6.3% at 2- and 3-years after transplantation 7 . However, islet transplantation is limited by a small donor pool and only available to the most brittle patients with unmanageable glycemic lability from the glucose monitoring, pump and/or intensive insulin injection therapy 5 . Therefore, solving the problem of islet donor shortage is the most urgent challenge now.…”